Non-invasive detection of phrenic nerve stimulation

ABSTRACT

Systems, methods, and graphical user interfaces are described herein for non-invasively detecting phrenic nerve stimulation during cardiac pacing therapy. Phrenic nerve stimulation information may be generated for one or more electrical pacing vectors at one or more power configurations. The phrenic nerve stimulation information may be displayed to a user for use in configuring and/or evaluating cardiac pacing therapy.

The disclosure herein relates to systems and methods for non-invasivedetection of phrenic nerve stimulation during delivering of cardiacpacing therapy. The system and methods may use a plurality of externalelectrodes proximate tissue of a patient to monitor electrical activityof the patient during cardiac pacing therapy and may use the monitoredelectrical activity to determine whether the cardiac pacing therapy isstimulating the phrenic nerve.

Cardiac pacing electrodes may be used in various systems, apparatus, andmethods for medical treatment of a patient. More specifically, cardiacpacing electrodes may be located adjacent, or in contact, with tissue(e.g., cardiac tissue, skin, etc.) of a patient to deliver cardiacpacing therapy to the patient using various different electrical pacingvectors. Some electrodes and/or electrical pacing vectors used forcardiac pacing therapy may inadvertently or unintentionally stimulatethe patient's phrenic nerve, e.g., causing undesired diaphragm movement,patient discomfort, etc.

Phrenic nerve stimulation detection has been disclosed in U.S. Pat. App.Pub. No. 2012/0296388 A1 filed on May 17, 2012 and entitled “PHRENICNERVE STIMULATION DETECTION USING HEART SOUNDS” and U.S. Pat. App. Pub.No. 2012/0296387 A1 filed on Nov. 22, 2012 and entitled “PHRENIC NERVESTIMULATION DETECTION USING HEART SOUNDS,” each of which is incorporatedherein by reference in their entirety.

SUMMARY

The exemplary systems and methods described herein may be configured todetermine whether a patient's phrenic nerve is being stimulated (e.g.,unintentionally or inadvertently stimulated) by pacing therapy. Morespecifically, the exemplary systems and methods may monitor electricalactivity using two or more external electrodes (e.g., proximate thetorso of a patient, in contact with the skin of the patient, etc.)during cardiac pacing therapy and may determine that the patient'sphrenic nerve is being stimulated based on the monitored electricalactivity.

The exemplary systems and methods may be used to test each of aplurality of different electrical pacing vectors (e.g., each differentelectrical pacing vector may use a different set of pacing electrodes)and may indicate to a user (e.g., a physician) which of the electricalpacing vectors stimulate the patient's phrenic nerve. Further, theexemplary systems and methods may be used to test each of a plurality ofdifferent power configurations for each different electrical pacingvector (e.g., each different power configuration may use a differentpulse width, voltage, number of pulses, etc.) and may indicate to a user(e.g., a physician) which of the power configurations for eachelectrical pacing vector stimulate the patient's phrenic nerve.

In one or more embodiments, a graphical user interface may be used todisplay phrenic nerve stimulation information such as, e.g., anindication of whether each of the electrical pacing vectors stimulatethe patient's phrenic nerve, the power configuration for each electricalpacing vector that stimulates the phrenic nerve, etc. The exemplarysystems and methods may be used during implant of pacing apparatus suchas an implantable medical device including one or more leads having, orcarrying, pacing electrodes. The exemplary systems and methods may bealso used during follow-up examinations after pacing apparatus hasalready been implanted or applied to a patient.

One exemplary non-invasive system may be configured for detectingphrenic nerve stimulation during pacing therapy using one or more pacingelectrodes of a plurality of pacing electrodes defining one or more ofelectrical pacing vectors. The exemplary system may include externalelectrode apparatus and computing apparatus coupled to the externalelectrode apparatus. The external electrode apparatus may include aplurality of external electrodes configured to be located proximatetissue of a patient (e.g., configured to be located on the anteriortorso of the patient). The computing apparatus may be configured tomonitor electrical activity using two or more external electrodes of theplurality of external electrodes during delivery of pacing therapy(e.g., monitoring for a selected time period after delivery of a pacingpulse such as, e.g., less than or equal to 250 milliseconds) using eachelectrical pacing vector of one or more electrical pacing vectors anddetermine whether the patient's phrenic nerve is stimulated by thepacing therapy delivered using each electrical pacing vector of the oneor more electrical pacing vectors based on the monitored electricalactivity.

In one or more embodiments, the external electrode apparatus may includeone of a band and a vest configured to be worn about the torso of thepatient and the plurality of external electrodes may be coupled to theband or vest.

In one or more embodiments, determining whether the patient's phrenicnerve is stimulated by the pacing therapy may include comparing amaximum peak-to-peak amplitude of the monitored electrical activity to athreshold value (e.g., greater than or equal to 30 millivolts, based onbaseline measurements, etc.).

In one or more embodiments, determining whether the patient's phrenicnerve is stimulated by the pacing therapy may include determining thatthe patient's phrenic nerve is stimulated if the monitored electricalactivity from a selected percentage of the two or more externalelectrodes used to monitor electrical activity during delivery of pacingtherapy is indicative of phrenic nerve stimulation.

In one or more embodiments, the system may include display apparatus.The display apparatus may include a graphical user interface configuredto present information for use in assisting a user in at least one ofevaluating pacing therapy and configuring pacing therapy. The computingapparatus may be coupled display apparatus and further configured todisplay, on the graphical user interface, phrenic nerve stimulationinformation for the one or more electrical pacing vectors for use inassisting a user in at least one of evaluating pacing therapy andconfiguring pacing therapy. In at least one embodiment, the phrenicnerve stimulation information is displayed proximate a graphicaldepiction of at least a portion of anatomy of the patient's heart (e.g.,blood vessel anatomy of the patient's heart).

In one or more embodiments, the delivery of pacing therapy using eachelectrical pacing vector of one or more electrical pacing vectors mayinclude delivery of pacing therapy using each electrical pacing vectorconfigured in each power configuration of a plurality of different powerconfigurations. In at least one embodiment, the computing apparatus maybe further configured to display, on a graphical user interface, powerconfiguration information for at least each electrical pacing vector ofthe one or more electrical pacing vectors that is determined tostimulate the patient's phrenic nerve.

One exemplary non-invasive method may be configured for detectingphrenic nerve stimulation during pacing therapy using one or more pacingelectrodes of a plurality of pacing electrodes defining one or more ofelectrical pacing vectors. The exemplary method may include monitoringelectrical activity of a patient using two or more external electrodesof a plurality of external electrodes during delivery of pacing therapyusing each electrical pacing vector of one or more electrical pacingvectors (e.g., where the plurality of external electrodes are locatedproximate tissue of the patient) and determining whether the patient'sphrenic nerve is stimulated by the pacing therapy delivered using eachelectrical pacing vector of the one or more electrical pacing vectorsbased on the monitored electrical activity. In at least one embodiment,the method may further include displaying, on a graphical userinterface, phrenic nerve stimulation information for the one or moreelectrical pacing vectors for use in assisting a user in at least one ofevaluating pacing therapy and configuring pacing therapy.

One exemplary non-invasive system may be configured for detectingphrenic nerve stimulation during pacing therapy using one or more pacingelectrodes of a plurality of pacing electrodes defining one or more ofelectrical pacing vectors. The exemplary system may include electrodemeans for monitoring electrical activity of a patient during delivery ofpacing therapy using each electrical pacing vector of one or moreelectrical pacing vectors and computing means for determining whetherthe patient's phrenic nerve is stimulated by the pacing therapydelivered using each electrical pacing vector of the one or moreelectrical pacing vectors based on monitored electrical activity. In atleast one embodiment, the system may further include display means fordisplaying, on a graphical user interface, phrenic nerve stimulationinformation for the one or more electrical pacing vectors for use inassisting a user in at least one of evaluating pacing therapy andconfiguring pacing therapy.

One exemplary electrode belt or vest for use in phrenic nervestimulation detection may include electrodes configured to be located onthe anterior torso surface as well as posterior torso surface of apatient. The exemplary electrode belt or vest may be used toautomatically detect phrenic nerve stimulation (PNS) during leftventricular (LV) and/or biventricular (BV) stimulation corresponding toa given pacing vector and pacing output. If PNS is present, then thedepolarization complexes monitored by electrodes on the anterior surface(e.g., electrodes closer to the diaphragm) may have augmented amplitudesdue to artifacts due to, or resulting from, the diaphragm movementcompared to the depolarization complexes monitored by electrodes on theposterior surface or compared to the same electrodes during LV and/or BVstimulation without PNS.

The exemplary methods and systems to detect phrenic nerve stimulationmay be automatic or automated. For example, an automated routine can beused that initiates LV/BV pacing at a short atrio-ventricular delay fora given LV pacing vector and given pacing outputs, segmentsdepolarization complexes from each ECG electrode during one or morecardiac cycle at rest with the patient in a given posture, extracts thepeak-to-peak amplitudes of the depolarization complex, and thenevaluates how many of the anterior electrodes have peak-to-peakamplitudes greater than a certain millivolt (mV) threshold. For example,an exemplary mV threshold may be about 30 mV, which may indicate highlyexaggerated amplitudes (e.g., typical amplitudes may be in the order ofabout 10 mV or less) that are attributable to artifacts from PNS. In atleast one embodiment, if more than a certain proportion (e.g., 80%) ofthe anterior electrodes exhibit exaggerated amplitudes (e.g., theamplitudes exceed a threshold, etc.), then PNS may be detected for thatparticular pacing vector and pacing output. In one or more embodiments,the information on presence/absence of PNS at a given pacing vector at agiven output may be stored and/or displayed.

Further, automated detection of PNS may be performed at varying pacingoutputs corresponding to a given LV pacing vector and the minimumoutputs at which PNS occurs corresponding to a given LV pacing vectormay also be stored/displayed. This PNS information may be used inconjunction with other information (e.g., impedance, thresholds,dyssynchrony information, battery longevity information, cardiacimprovement information, etc.) to assist a user in selecting, ordeciding on, an optimal LV pacing vector for use in pacing therapy.Further, the detection of PNS for a given LV pacing vector may berepeated for different resting postures of the patient (e.g., supine,lying on right side, lying on left side, etc.). Additionally, exemplaryautomated routines to detect PNS during implant and/or follow-up may beintegrated with automated routines for LV capture management to assist auser in identifying, or finding, an optimal pacing vector for affectingbetter patient response.

In at least one embodiment, instead of looking at absolute values ofpeak-to-peak amplitudes, a ratio of peak-to-peak depolarizationamplitudes during LV/BV stimulation may be compared to peak-to-peakdepolarization amplitudes during baseline rhythm (e.g., that does notinvolve left ventricular pacing). If more than a certain proportion(e.g., 80%) of anterior electrodes exhibit a high ratio (e.g., greaterthan 5) when compared to the baseline values, PNS may be detected forLV/BV stimulation.

The above summary is not intended to describe each embodiment or everyimplementation of the present disclosure. A more complete understandingwill become apparent and appreciated by referring to the followingdetailed description and claims taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram of an exemplary system including an exemplaryimplantable medical device (IMD).

FIG. 2A is a diagram of the exemplary IMD of FIG. 1.

FIG. 2B is a diagram of an enlarged view of a distal end of theelectrical lead disposed in the left ventricle of FIG. 2A.

FIG. 3A is a block diagram of an exemplary IMD, e.g., the IMD of FIGS.1-2.

FIG. 3B is another block diagram of an exemplary IMD (e.g., animplantable pulse generator) circuitry and associated leads employed inthe system of FIGS. 1-2 for providing three sensing channels andcorresponding pacing channels.

FIG. 4 is a diagram of an exemplary system including electrodeapparatus, imaging apparatus, display apparatus, and computingapparatus.

FIGS. 5A-5B are conceptual diagrams illustrating exemplary systems formeasuring torso-surface potentials.

FIG. 6 is a block diagram of an exemplary method of identifying anoptimal electrical vector.

FIG. 7 is an exemplary graphical user interface depicting a table ofcardiac improvement information for a plurality of electrodes.

FIG. 8 is another exemplary graphical user interface depicting a tableof cardiac improvement information for a plurality of electrodes.

FIG. 9 is an exemplary graphical user interface depicting a table oflongevity information for a plurality of electrode vectors.

FIG. 10 is an exemplary graphical user interface depicting a table oflongevity information, phrenic nerve stimulation, and cardiacimprovement information for a plurality of electrical vectors.

FIG. 11 is an exemplary graphical user interface depicting a graphicalrepresentation of a pair of leads and cardiac improvement informationand longevity information depicted proximate the electrodes of theleads.

FIG. 12 is an exemplary graphical user interface depicting blood vesselanatomy configured to assist a user in navigating an implantableelectrode to a region of a patient's heart for cardiac therapy.

FIG. 13 is an exemplary graphical user interface depicting a human heartincluding activation times mapped thereon configured to assist a user innavigating an implantable electrode to a region of a patient's heart forcardiac therapy.

FIG. 14 is a block diagram of an exemplary method of detecting phrenicnerve stimulation.

FIG. 15 is a graph of electrical signals monitored over time usingmultiple external electrodes coupled to a patient that is not undergoingphrenic nerve stimulation.

FIG. 16 is a graph of electrical signals monitored over time usingmultiple external electrodes coupled to a patient that is undergoingphrenic nerve stimulation.

FIG. 17 depicts graphical representations of electrical activity of apatient that is not undergoing phrenic nerve stimulation.

FIG. 18 depicts graphical representations of electrical activity of apatient that is undergoing phrenic nerve stimulation.

FIG. 19 depicts graphical representations of electrical activity of apatient that is undergoing phrenic nerve stimulation and is notundergoing phrenic nerve stimulation.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

In the following detailed description of illustrative embodiments,reference is made to the accompanying figures of the drawing which forma part hereof, and in which are shown, by way of illustration, specificembodiments which may be practiced. It is to be understood that otherembodiments may be utilized and structural changes may be made withoutdeparting from (e.g., still falling within) the scope of the disclosurepresented hereby.

Exemplary systems, methods, and interfaces shall be described withreference to FIGS. 1-19. It will be apparent to one skilled in the artthat elements or processes from one embodiment may be used incombination with elements or processes of the other embodiments, andthat the possible embodiments of such systems, methods, and interfacesusing combinations of features set forth herein is not limited to thespecific embodiments shown in the Figures and/or described herein.Further, it will be recognized that the embodiments described herein mayinclude many elements that are not necessarily shown to scale. Stillfurther, it will be recognized that timing of the processes and the sizeand shape of various elements herein may be modified but still fallwithin the scope of the present disclosure, although certain timings,one or more shapes and/or sizes, or types of elements, may beadvantageous over others.

As described herein, various exemplary systems, methods, and interfacesmay utilize electrodes configured to sense one or more electricalsignals (e.g., depolarization complexes, etc.) from the tissue of apatient (e.g., the skin about the torso of the patient) and/or delivertherapy to tissue of the patient (e.g., cardiac tissue of the patient).For example, external electrodes configured for sensing may be locatedon the skin of the patient's torso. Further, for example, electrodesconfigured for delivering pacing therapy may be included as part of animplantable medical device (IMD) and located on one or more leadsconfigured to be located proximate one or more portions of a patient'sheart.

The exemplary methods and processes described herein may be utilized andimplemented by one or more (e.g., two or more, a plurality, etc.)systems, apparatus, interfaces, and devices that include and/or arecoupled to one or more sensing electrodes. Additionally, the exemplarymethods and processes may be used in conjunction with an exemplarytherapy system 10 described herein with reference to FIGS. 1-3. Further,the exemplary methods and processes may use the exemplary system 100including a spatial electrode-array as described herein with referenceto FIGS. 5A-5B to sense one or more electrical signals of a patient.Although only therapy system 10 and sensing system 100 are described anddepicted herein, it is to be understood that the exemplary methods andprocesses may be used by any system including computing apparatuscapable of analyzing signals from one or more electrodes. The computingapparatus, for example, may be located in an external computer orprogrammer, may be located in an IMD, or may be located in a serverattached to a network.

FIG. 1 is a conceptual diagram illustrating an exemplary therapy system10 that may be used to deliver pacing therapy to a patient 14. Patient14 may, but not necessarily, be a human. The therapy system 10 mayinclude an implantable medical device 16 (IMD), which may be coupled toleads 18, 20, 22 and/or a programmer 24. The IMD 16 may be, e.g., animplantable pacemaker, cardioverter, and/or defibrillator, that provideselectrical signals to the heart 12 of the patient 14 via electrodescoupled to one or more of the leads 18, 20, 22.

The leads 18, 20, 22 extend into the heart 12 of the patient 14 to senseelectrical activity of the heart 12 and/or to deliver electricalstimulation to the heart 12. In the example shown in FIG. 1, the rightventricular (RV) lead 18 extends through one or more veins (not shown),the superior vena cava (not shown), and the right atrium 26, and intothe right ventricle 28. The left ventricular (LV) coronary sinus lead 20extends through one or more veins, the vena cava, the right atrium 26,and into the coronary sinus 30 to a region adjacent to the free wall ofthe left ventricle 32 of the heart 12 (in other embodiments, the LV lead20 may be placed in the LV endocardium). The right atrial (RA) lead 22extends through one or more veins and the vena cava, and into the rightatrium 26 of the heart 12.

The IMD 16 may sense, among other things, electrical signals attendantto the depolarization and repolarization of the heart 12 via electrodescoupled to at least one of the leads 18, 20, 22. The IMD 16 may beconfigured to provide pacing therapy (e.g., pacing pulses) to the heart12 based on the electrical signals sensed within the heart 12. Further,the IMD 16 may be operable to adjust one or more parameters associatedwith the pacing therapy such as, e.g., AV delay and other varioustimings, pulse width, amplitude, voltage, burst length, etc. Further,the IMD 16 may be operable to use various electrode configurations todeliver pacing therapy, which may be unipolar, bipolar, quadripoloar, orfurther multipolar. For example, a multipolar lead may include severalelectrodes which can be used for delivering pacing therapy. Hence, amultipolar lead system may provide, or offer, multiple electricalvectors to pace from. A pacing vector may include at least one cathode,which may be at least one electrode located on at least one lead, and atleast one anode, which may be at least one electrode located on at leastone lead (e.g., the same lead, or a different lead) and/or on thecasing, or can, of the IMD. While improvement in cardiac function as aresult of the pacing therapy may primarily depend on the cathode, theelectrical parameters like impedance, pacing threshold voltage, currentdrain, longevity, etc. may be more dependent on the pacing vector, whichincludes both the cathode and the anode. The IMD 16 may also providedefibrillation therapy and/or cardioversion therapy via electrodeslocated on at least one of the leads 18, 20, 22. Further, the IMD 16 maydetect arrhythmia of the heart 12, such as fibrillation of theventricles 28, 32, and deliver defibrillation therapy to the heart 12 inthe form of electrical pulses. In some examples, IMD 16 may beprogrammed to deliver a progression of therapies, e.g., pulses withincreasing energy levels, until a fibrillation of the heart 12 isstopped.

In some examples, a programmer 24, which may be a handheld computingdevice or a computer workstation, may be used by a user, such as aphysician, technician, another clinician, and/or patient, to communicatewith the IMD 16 (e.g., to program the IMD 16). For example, the user mayinteract with the programmer 24 to retrieve information concerningphrenic nerve stimulation information for one or more electrical pacingvectors (e.g., whether one or more electrical pacing vectors stimulatethe phrenic nerve, the power configuration at which one or moreelectrical pacing vectors stimulate the phrenic nerve, etc.), cardiacimprovement information (e.g., dyssynchrony information, etc.) for oneor more electrodes, and longevity information (e.g., capture thresholdinformation, impedance values, etc.). Additionally, the user mayinteract with the programmer 24 to select one or more electricalvectors, e.g., for use in delivering therapy. Further, the user mayinteract with the programmer 24 to retrieve information concerning oneor more detected or indicated faults associated within the IMD 16 and/orthe pacing therapy delivered therewith. For instance, computingapparatus located in one or both of the IMD 16 and the programmer 24 maybe configured to analyze or evaluate signals from one or more electrodesto select one or more electrodes and identify one or more optimalelectrical vectors. The IMD 16 and the programmer 24 may communicate viawireless communication using any techniques known in the art. Examplesof communication techniques may include, e.g., low frequency orradiofrequency (RF) telemetry, but other techniques are alsocontemplated.

FIG. 2A is a conceptual diagram illustrating the IMD 16 and the leads18, 20, 22 of therapy system 10 of FIG. 1 in more detail. The leads 18,20, 22 may be electrically coupled to a therapy delivery module (e.g.,for delivery of pacing therapy using one or more electrodes), a sensingmodule (e.g., for sensing one or more signals from one or moreelectrodes), and/or any other modules of the IMD 16 via a connectorblock 34. In some examples, the proximal ends of the leads 18, 20, 22may include electrical contacts that are electrically coupled torespective electrical contacts within the connector block 34 of the IMD16. In addition, in some examples, the leads 18, 20, 22 may bemechanically coupled to the connector block 34 with the aid of setscrews, connection pins, or another suitable mechanical couplingmechanism.

Each of the leads 18, 20, 22 includes an elongated insulative lead body,which may carry a number of conductors (e.g., concentric coiledconductors, straight conductors, etc.) separated from one another byinsulation (e.g., tubular insulative sheaths). In the illustratedexample, bipolar electrodes 40, 42 are located proximate to a distal endof the lead 18. In addition, the bipolar electrodes 44, 45, 46, 47 arelocated proximate to a distal end of the lead 20 and the bipolarelectrodes 48, 50 are located proximate to a distal end of the lead 22.

The electrodes 40, 44, 45, 46, 47, 48 may take the form of ringelectrodes, and the electrodes 42, 50 may take the form of extendablehelix tip electrodes mounted retractably within the insulative electrodeheads 52, 54, 56, respectively. Each of the electrodes 40, 42, 44, 45,46, 47, 48, 50 may be electrically coupled to a respective one of theconductors (e.g., coiled and/or straight) within the lead body of itsassociated lead 18, 20, 22, and thereby coupled to respective ones ofthe electrical contacts on the proximal end of the leads 18, 20, 22.

In at least one embodiment, electrodes 44, 45, 46 47 may have anelectrode surface area of about 5.3 mm² to about 5.8 mm². Electrodes 44,45, 46, and 47 may also referred to as LV1, LV2, LV3, and LV4,respectively. The LV electrodes (i.e., left ventricle electrode 1 (LV1)44, left ventricle electrode 2 (LV2) 45, left ventricle electrode 3(LV3) 46, left ventricle 4 (LV4) 47, etc.) on the lead 20 can be spacedapart at variable distances. For example, electrode 44 may be a distanceof, e.g., about 21 millimeters (mm) away from electrode 45, electrodes45, 46 may be spaced a distance of, e.g., about 1.3 mm to about 1.5 mmaway from each other, and electrodes 46, 47 may be spaced a distance of,e.g., about 20 mm to about 21 mm away from each other.

The electrodes 40, 42, 44, 45, 46, 47, 48, 50 may further be used tosense electrical signals (e.g., morphological waveforms withinelectrograms (EGM)) attendant to the depolarization and repolarizationof the heart 12. The sensed electrical signals may be used to determinewhich of the electrodes 40, 42, 44, 45, 46, 47, 48, 50 are the mosteffective in improving cardiac function. The electrical signals areconducted to the IMD 16 via the respective leads 18, 20, 22. In someexamples, the IMD 16 may also deliver pacing pulses via the electrodes40, 42, 44, 45, 46, 47, 48, 50 to cause depolarization of cardiac tissueof the patient's heart 12. In some examples, as illustrated in FIG. 2A,the IMD 16 includes one or more housing electrodes, such as housingelectrode 58, which may be formed integrally with an outer surface of ahousing 60 (e.g., hermetically-sealed housing) of the IMD 16 orotherwise coupled to the housing 60. Any of the electrodes 40, 42, 44,45, 46, 47, 48 and 50 may be used for unipolar pacing or sensing incombination with housing electrode 58. In other words, any of electrodes40, 42, 44, 45, 46, 47, 48, 50, 58 may be used in combination to form anelectrical pacing vector, e.g., a pacing vector that may be used todeliver pacing therapy to a patient's heart. It is generally understoodby those skilled in the art that other electrodes can also be selectedto define, or be used for, pacing and sensing vectors. Further, any ofelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, which are not being usedto deliver pacing therapy, may be used to sense electrical activityduring pacing therapy.

As described in further detail with reference to FIGS. 3A-3B, thehousing 60 may enclose a therapy delivery module that may include astimulation generator for generating cardiac pacing pulses anddefibrillation or cardioversion shocks as well as a sensing module formonitoring the patient's heart rhythm. The leads 18, 20, 22 may alsoinclude elongated electrodes 62, 64, 66, respectively, which may takethe form of a coil. The IMD 16 may deliver defibrillation shocks to theheart 12 via any combination of the elongated electrodes 62, 64, 66 andthe housing electrode 58. The electrodes 58, 62, 64, 66 may also be usedto deliver cardioversion pulses to the heart 12. Further, the electrodes62, 64, 66 may be fabricated from any suitable electrically conductivematerial, such as, but not limited to, platinum, platinum alloy, and/orother materials known to be usable in implantable defibrillationelectrodes. Since electrodes 62, 64, 66 are not generally configured todeliver pacing therapy, any of electrodes 62, 64, 66 may be used tosense electrical activity (e.g., for use in determining electrodeeffectiveness, for use in analyzing pacing therapy effectiveness, etc.)and may be used in combination with any of electrodes 40, 42, 44, 45,46, 47, 48, 50, 58. In at least one embodiment, the RV elongatedelectrode 62 may be used to sense electrical activity of a patient'sheart during the delivery of pacing therapy (e.g., in combination withthe housing electrode 58 forming a RV elongated coil, or defibrillationelectrode, to housing electrode vector).

The configuration of the exemplary therapy system 10 illustrated inFIGS. 1-2 is merely one example. In other examples, the therapy systemmay include epicardial leads and/or patch electrodes instead of, or inaddition to, the transvenous leads 18, 20, 22 illustrated in FIG. 1.Further, in one or more embodiments, the IMD 16 need not be implantedwithin the patient 14. For example, the IMD 16 may deliver variouscardiac therapies to the heart 12 via percutaneous leads that extendthrough the skin of the patient 14 to a variety of positions within, oroutside of, the heart 12. In one or more embodiments, the system 10 mayutilize wireless pacing (e.g., using energy transmission to theintracardiac pacing component(s) via ultrasound, inductive coupling, RF,etc.) and sensing cardiac activation using electrodes on the can/housingand/or on subcutaneous leads.

In other examples of therapy systems that provide electrical stimulationtherapy to the heart 12, such therapy systems may include any suitablenumber of leads coupled to the IMD 16, and each of the leads may extendto any location within or proximate to the heart 12. For example, otherexamples of therapy systems may include three transvenous leads locatedas illustrated in FIGS. 1-2. Still further, other therapy systems mayinclude a single lead that extends from the IMD 16 into the right atrium26 or the right ventricle 28, or two leads that extend into a respectiveone of the right atrium 26 and the right ventricle 28.

FIG. 3A is a functional block diagram of one exemplary configuration ofthe IMD 16. As shown, the IMD 16 may include a control module 81, atherapy delivery module 84 (e.g., which may include a stimulationgenerator), a sensing module 86, and a power source 90.

The control module 81 may include a processor 80, memory 82, and atelemetry module 88. The memory 82 may include computer-readableinstructions that, when executed, e.g., by the processor 80, cause theIMD 16 and/or the control module 81 to perform various functionsattributed to the IMD 16 and/or the control module 81 described herein.Further, the memory 82 may include any volatile, non-volatile, magnetic,optical, and/or electrical media, such as a random access memory (RAM),read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasableprogrammable ROM (EEPROM), flash memory, and/or any other digital media.An exemplary capture management module may be the left ventricularcapture management (LVCM) module described in U.S. Pat. No. 7,684,863entitled “LV THRESHOLD MEASUREMENT AND CAPTURE MANAGEMENT” and issuedMar. 23, 2010, which is incorporated herein by reference in itsentirety.

The processor 80 of the control module 81 may include any one or more ofa microprocessor, a controller, a digital signal processor (DSP), anapplication specific integrated circuit (ASIC), a field-programmablegate array (FPGA), and/or equivalent discrete or integrated logiccircuitry. In some examples, the processor 80 may include multiplecomponents, such as any combination of one or more microprocessors, oneor more controllers, one or more DSPs, one or more ASICs, and/or one ormore FPGAs, as well as other discrete or integrated logic circuitry. Thefunctions attributed to the processor 80 herein may be embodied assoftware, firmware, hardware, or any combination thereof.

The control module 81 may be used to determine the effectiveness of theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 using theexemplary methods and/or processes described herein according to aselected one or more programs, which may be stored in the memory 82.Further, the control module 81 may control the therapy delivery module84 to deliver therapy (e.g., electrical stimulation therapy such aspacing) to the heart 12 according to a selected one or more therapyprograms, which may be stored in the memory 82. More, specifically, thecontrol module 81 (e.g., the processor 80) may control variousparameters of the electrical stimulus delivered by the therapy deliverymodule 84 such as, e.g., AV delays, pacing pulses with the amplitudes,pulse widths, frequency, or electrode polarities, etc., which may bespecified by one or more selected therapy programs (e.g., phrenic nervestimulation detection programs, AV delay adjustment programs, pacingtherapy programs, pacing recovery programs, capture management programs,etc.). As shown, the therapy delivery module 84 is electrically coupledto electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66, e.g., viaconductors of the respective lead 18, 20, 22, or, in the case of housingelectrode 58, via an electrical conductor disposed within housing 60 ofIMD 16. Therapy delivery module 84 may be configured to generate anddeliver electrical stimulation therapy such as pacing therapy to theheart 12 using one or more of the electrodes 40, 42, 44, 45, 46, 47, 48,50, 58, 62, 64, 66.

For example, therapy delivery module 84 may deliver pacing stimulus(e.g., pacing pulses) via ring electrodes 40, 44, 45, 46, 47, 48 coupledto leads 18, 20, 22, respectively, and/or helical tip electrodes 42, 50of leads 18, 22. Further, for example, therapy delivery module 84 maydeliver defibrillation shocks to heart 12 via at least two of electrodes58, 62, 64, 66. In some examples, therapy delivery module 84 may beconfigured to deliver pacing, cardioversion, or defibrillationstimulation in the form of electrical pulses. In other examples, therapydelivery module 84 may be configured deliver one or more of these typesof stimulation in the form of other signals, such as sine waves, squarewaves, and/or other substantially continuous time signals.

The IMD 16 may further include a switch module 85 and the control module81 (e.g., the processor 80) may use the switch module 85 to select,e.g., via a data/address bus, which of the available electrodes are usedto deliver therapy such as pacing pulses for pacing therapy, or which ofthe available electrodes are used for sensing. The switch module 85 mayinclude a switch array, switch matrix, multiplexer, or any other type ofswitching device suitable to selectively couple the sensing module 86and/or the therapy delivery module 84 to one or more selectedelectrodes. More specifically, the therapy delivery module 84 mayinclude a plurality of pacing output circuits. Each pacing outputcircuit of the plurality of pacing output circuits may be selectivelycoupled, e.g., using the switch module 85, to one or more of theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 (e.g., a pairof electrodes for delivery of therapy to a pacing vector). In otherwords, each electrode can be selectively coupled to one of the pacingoutput circuits of the therapy delivery module using the switchingmodule 85.

The sensing module 86 is coupled (e.g., electrically coupled) to sensingapparatus, which may include, among additional sensing apparatus, theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 to monitorelectrical activity of the heart 12, e.g., electrocardiogram(ECG)/electrogram (EGM) signals, etc. The ECG/EGM signals may be used toidentify the effectiveness of each of the electrodes 40, 42, 44, 45, 46,47, 48, 50, 58, 62, 64, 66 (e.g., by monitoring or measuring the signalsfor analysis by the control module 81, the programmer 24, etc.).Further, the ECG/EGM signals may be used to measure or monitoractivation times (e.g., ventricular activations times, etc.), heart rate(HR), heart rate variability (HRV), heart rate turbulence (HRT),deceleration/acceleration capacity, deceleration sequence incidence,T-wave alternans (TWA), P-wave to P-wave intervals (also referred to asthe P-P intervals or A-A intervals), R-wave to R-wave intervals (alsoreferred to as the R-R intervals or V-V intervals), P-wave to QRScomplex intervals (also referred to as the P-R intervals, A-V intervals,or P-Q intervals), QRS-complex morphology, ST segment (i.e., the segmentthat connects the QRS complex and the T-wave), T-wave changes, QTintervals, electrical vectors, etc.

The switch module 85 may be also be used with the sensing module 86 toselect which of the available electrodes are used, or enabled, to, e.g.,sense electrical activity of the patient's heart (e.g., one or moresensing electrical vectors of the patient's heart may use anycombination of the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62,64, 66). Likewise, the switch module 85 may be also be used with thesensing module 86 to select which of the available electrodes are not tobe used (e.g., disabled) to, e.g., sense electrical activity of thepatient's heart. In some examples, the control module 81 may select theelectrodes that function as sensing electrodes via the switch modulewithin the sensing module 86, e.g., by providing signals via adata/address bus.

In some examples, sensing module 86 includes a channel that includes anamplifier with a relatively wider pass band than the R-wave or P-waveamplifiers. Signals from the selected sensing electrodes may be providedto a multiplexer, and thereafter converted to multi-bit digital signalsby an analog-to-digital converter for storage in memory 82, e.g., as anelectrogram (EGM). In some examples, the storage of such EGMs in memory82 may be under the control of a direct memory access circuit. Thecontrol module 81 (e.g., using the processor 80) may employ digitalsignal analysis techniques to characterize the digitized signals storedin memory 82 and to analyze one or more morphological waveforms of theEGM signals to determine pacing therapy effectiveness, etc. For example,the processor 80 may be configured to determine, or obtain, one morefeatures of one or more sensed morphological waveforms within one ofmore electrical vectors of the patient's heart and store the one or morefeatures within the memory 82 for use in comparing features, values,etc. of the waveforms to determine effectiveness of the electrodes.

In some examples, the control module 81 may operate as an interruptdriven device, and may be responsive to interrupts from a pacer timingand control module, where the interrupts may correspond to theoccurrences of sensed P-waves and R-waves and the generation of cardiacpacing pulses. Any necessary mathematical calculations may be performedby the processor 80 and any updating of the values or intervalscontrolled by the pacer timing and control module may take placefollowing such interrupts. A portion of memory 82 may be configured as aplurality of recirculating buffers, capable of holding one or moreseries of measured intervals, which may be analyzed by, e.g., theprocessor 80 in response to the occurrence of a pace or sense interruptto determine whether the patient's heart 12 is presently exhibiting anyarrhythmia (e.g., atrial or ventricular tachyarrhythmia).

The telemetry module 88 of the control module 81 may include anysuitable hardware, firmware, software, or any combination thereof forcommunicating with another device, such as the programmer 24 asdescribed herein with respect to FIG. 1. For example, under the controlof the processor 80, the telemetry module 88 may receive downlinktelemetry from and send uplink telemetry to the programmer 24 with theaid of an antenna, which may be internal and/or external. The processor80 may provide data to be uplinked to the programmer 24 and the controlsignals for the telemetry circuit within the telemetry module 88, e.g.,via an address/data bus. In some examples, the telemetry module 88 mayprovide received data to the processor 80 via a multiplexer.

The various components of the IMD 16 are further coupled to a powersource 90, which may include a rechargeable or non-rechargeable battery.A non-rechargeable battery may be selected to last for several years,while a rechargeable battery may be charged (e.g., inductively charged)from an external device, e.g., on a daily or weekly basis.

FIG. 3B is another embodiment of a functional block diagram for IMD 16.FIG. 3B depicts bipolar RA lead 22, bipolar RV lead 18, and bipolar LVCS lead 20 without the LA CS pace/sense electrodes and coupled with animplantable pulse generator (IPG) circuit 31 having programmable modesand parameters of a bi-ventricular DDD/R type. In turn, the sensorsignal processing circuit 91 may be indirectly coupled to the timingcircuit 83 and via data and control bus to microcomputer circuitry 33.The IPG circuit 31 is illustrated in a functional block diagram dividedgenerally into a microcomputer circuit 33 and a pacing circuit 21. Thepacing circuit 21 includes the digital controller/timer circuit 83, theoutput amplifiers circuit 51, the sense amplifiers circuit 55, the RFtelemetry transceiver 41, the activity sensor circuit 35 as well as anumber of other circuits and components described below.

Crystal oscillator circuit 89 provides the basic timing clock for thepacing circuit 21 while a battery 29 provides power. Power-on-resetcircuit 87 may responds to an initial connection of the circuit to thebattery for defining an initial operating condition, and similarly, mayreset the operative state of the device in response to detection of alow battery condition. Reference mode circuit 37 may generate stablevoltage reference and currents for the analog circuits within the pacingcircuit 21 while analog to digital converter ADC and multiplexer circuit39 may digitize analog signals and voltages to provide real timetelemetry of cardiac signals from sense amplifiers 55 for uplinktransmission via RF transmitter and receiver circuit 41.

If the IPG circuit 31 is programmed to a rate responsive mode, thesignals output by one or more physiologic sensor may be employed as arate control parameter (RCP) to derive a physiologic escape interval.For example, the escape interval may be adjusted proportionally to thepatient's activity level developed in the patient activity sensor (PAS)circuit 35 in the depicted, exemplary IPG circuit 31. The patientactivity sensor 27 may be coupled to the IPG housing and may take theform of a piezoelectric crystal transducer and its output signal may beprocessed and used as the RCP. Sensor 27 may generate electrical signalsin response to sensed physical activity that are processed by activitycircuit 35 and provided to digital controller/timer circuit 83. Activitycircuit 35 and associated sensor 27 may correspond to the circuitrydisclosed in U.S. Pat. No. 5,052,388 entitled “METHOD AND APPARATUS FORIMPLEMENTING ACTIVITY SENSING IN A PULSE GENERATOR” and issued on Oct.1, 1991 and U.S. Pat. No. 4,428,378 entitled “RATE ADAPTIVE PACER” andissued on Jan. 31, 1984, each of which is incorporated herein byreference in its entirety. Similarly, the exemplary systems, apparatus,and methods described herein may be practiced in conjunction withalternate types of sensors such as oxygenation sensors, pressuresensors, pH sensors and respiration sensors, etc. Alternately, QT timemay be used as the rate indicating parameter. Similarly, the exemplaryembodiments described herein may also be practiced in non-rateresponsive pacemakers.

Data transmission to and from the external programmer may beaccomplished by way of a telemetry antenna 57 and an associated RFtransceiver 41, which may serve both to demodulate received downlinktelemetry and to transmit uplink telemetry. Uplink telemetrycapabilities may typically include the ability to transmit storeddigital information such as, e.g., operating modes and parameters, EGMhistograms, and other events, as well as real time EGMs of atrial and/orventricular electrical activity and marker channel pulses indicating theoccurrence of sensed and paced depolarizations in the atrium andventricle.

Microcomputer circuit 33 may contain, or include, a microprocessor 80and associated system clock and on-processor RAM chip 82A and ROM chip82B, respectively. In addition, microcomputer circuit 33 includes aseparate RAM/ROM chip 82C to provide additional memory capacity.Microprocessor 80 may normally operate in a reduced power consumptionmode and may be interrupt driven. For example, the microprocessor 80 mayawakened in response to defined interrupt events, which may includeA-TRIG, RV-TRIG, and LV-TRIG signals generated by timers in digitaltimer/controller circuit 83 and A-EVENT, RV-EVENT, and LV-EVENT signalsgenerated by sense amplifiers circuit 55, etc. The specific values ofthe intervals and delays timed out by digital controller/timer circuit83 may be controlled by the microcomputer circuit 33 by way of data andcontrol bus from programmed-in parameter values and operating modes. Inaddition, if programmed to operate as a rate responsive pacemaker, atimed interrupt, e.g., every cycle or every two seconds, may be providedin order to allow the microprocessor to analyze the activity sensor dataand update the basic A-A, V-A, or V-V escape interval, as applicable. Inaddition, the microprocessor 80 may also serve to define variable,operative AV delay intervals and the energy delivered to each ventricle.

In one embodiment, microprocessor 80 is a custom microprocessor adaptedto fetch and execute instructions stored in RAM/ROM unit 82 in aconventional manner. It is contemplated, however, that otherimplementations may be suitable to practice the present disclosure. Forexample, an off-the-shelf, commercially available microprocessor ormicrocontroller, or custom application-specific, hardwired logic, orstate-machine type circuit may perform the functions of microprocessor80.

Digital controller/timer circuit 83 may operate under the generalcontrol of the microcomputer 33 to control timing and other functionswithin the pacing circuit 21 and may include a set of timing andassociated logic circuits. The depicted timing circuits include URI/LRItimers 83A, V-V delay timer 83B, intrinsic interval timers 83C fortiming elapsed V-EVENT to V-EVENT intervals or V-EVENT to A-EVENTintervals or the V-V conduction interval, escape interval timers 83D fortiming A-A, V-A, and/or V-V pacing escape intervals, an AV delayinterval timer 83E for timing the A-LVp delay (or A-RVp delay) from apreceding A-EVENT or A-TRIG, a post-ventricular timer 83F for timingpost-ventricular time periods, and a date/time clock 83G.

The AV delay interval timer 83E may be loaded with an appropriate delayinterval for one ventricular chamber (e.g., either an A-RVp delay or anA-LVp delay) to time-out starting from a preceding A-PACE or A-EVENT.The interval timer 83E may trigger pacing stimulus delivery and can bebased on one or more prior cardiac cycles (or from a data setempirically derived for a given patient).

The post-event timer 83F may be configured to time out thepost-ventricular time period following an RV-EVENT, LV-EVENT, RV-TRIG,or LV-TRIG and post-atrial time periods following an A-EVENT or A-TRIG.The durations of the post-event time periods may also be selected asprogrammable parameters stored in the microcomputer 33. Thepost-ventricular time periods include the PVARP, a post-atrialventricular blanking period (PAVBP), a ventricular blanking period(VBP), a post-ventricular atrial blanking period (PVARP) and aventricular refractory period (VRP) although other periods can besuitably defined depending, at least in part, on the operative circuitryemployed in the pacing engine. The post-atrial time periods include anatrial refractory period (ARP) during which an A-EVENT is ignored forthe purpose of resetting any AV delay, and an atrial blanking period(ABP) during which atrial sensing is disabled. It should be noted thatthe starting of the post-atrial time periods and the AV delays can becommenced substantially simultaneously with the start or end of eachA-EVENT or A-TRIG or, in the latter case, upon the end of the A-PACEwhich may follow the A-TRIG. Similarly, the starting of thepost-ventricular time periods and the V-A escape interval can becommenced substantially simultaneously with the start or end of theV-EVENT or V-TRIG or, in the latter case, upon the end of the V-PACEwhich may follow the V-TRIG. The microprocessor 80 may also optionallycalculate AV delays, post-ventricular time periods, and post-atrial timeperiods that vary with the sensor based escape interval established inresponse to the RCP(s) and/or with the intrinsic atrial rate.

The output amplifiers circuit 51 may include a RA pace pulse generator(and a LA pace pulse generator if LA pacing is provided), a RV pacepulse generator, and a LV pace pulse generator. In order to triggergeneration of an RV-PACE or LV-PACE pulse, digital controller/timercircuit 83 generates the RV-TRIG signal at the time-out of the A-RVpdelay (in the case of RV pre-excitation) or the LV-TRIG at the time-outof the A-LVp delay (in the case of LV pre-excitation) provided by AVdelay interval timer 83E (or the V-V delay timer 83B). Similarly,digital controller/timer circuit 83 generates a RA-TRIG signal thattriggers output of a RA-PACE pulse (or an LA-TRIG signal that triggersoutput of an LA-PACE pulse, if provided) at the end of the V-A escapeinterval timed by escape interval timers 83D.

The output amplifier circuit 51 may include switching circuits forcoupling selected pace electrode pairs from among the lead conductorsand the IND_CAN electrode 20 to the RA pace pulse generator (and LA pacepulse generator if provided), RV pace pulse generator and LV pace pulsegenerator. Pace/sense electrode pair selection and control circuit 53may select lead conductors and associated pace electrode pairs to becoupled with the atrial and ventricular output amplifiers within outputamplifiers circuit 51 for accomplishing RA, LA, RV, and LV pacing.

The sense amplifier circuit 55 may include sense amplifiers such as,e.g., high impedance P-wave and R-wave sense amplifiers that may be usedto amplify a voltage difference signal that is generated across thesense electrode pairs by the passage of cardiac depolarizationwavefronts. High impedance sense amplifiers may further use high gain toamplify low amplitude signals and may rely on pass band filters, timedomain filtering, and amplitude threshold comparison to discriminate aP-wave or R-wave from background electrical noise. Digitalcontroller/timer circuit 83 may further control sensitivity settings ofthe atrial and ventricular sense amplifiers 55.

The sense amplifiers may be typically uncoupled from the senseelectrodes during blanking periods before, during, and after delivery ofa pace pulse to any of the pace electrodes of the pacing system to avoidsaturation of the sense amplifiers. The sense amplifier circuit 55 mayinclude blanking circuits for uncoupling the selected pairs of the leadconductors and the IND-CAN electrode 20 from the inputs of the RA senseamplifier (and LA sense amplifier if provided), RV sense amplifier andLV sense amplifier during the ABP, PVABP and VBP. The sense amplifierscircuit 55 may also include switching circuits for coupling selectedsense electrode lead conductors and the IND-CAN electrode 20 to the RAsense amplifier (and LA sense amplifier if provided), RV sense amplifierand LV sense amplifier. Again, sense electrode selection and controlcircuit 53 may select conductors and associated sense electrode pairs tobe coupled with the atrial and ventricular sense amplifiers within theoutput amplifiers circuit 51 and sense amplifiers circuit 55 foraccomplishing RA, LA, RV, and LV sensing along desired unipolar andbipolar sensing vectors.

Right atrial depolarizations or P-waves in the A-SENSE signal that aresensed by the A sense amplifier result in a RA-EVENT signal that iscommunicated to the digital controller/timer circuit 83. Similarly, leftatrial depolarizations or P-waves in a LA-SENSE signal may be sensed bya LA sense amplifier, if provided, and may result in a LA-EVENT signalthat is communicated to the digital controller/timer circuit 83.Ventricular depolarizations or R-waves in the RV-SENSE signal are sensedby a ventricular sense amplifier result in an RV-EVENT signal that iscommunicated to the digital controller/timer circuit 83. Similarly,ventricular depolarizations or R-waves in the LV-SENSE signal are sensedby a ventricular sense amplifier result in an LV-EVENT signal that iscommunicated to the digital controller/timer circuit 83. The RV-EVENT,LV-EVENT, RA-EVENT, and/or LA-EVENT signals may be refractory ornon-refractory, and can inadvertently be triggered by electrical noisesignals or aberrantly conducted depolarization waves rather than trueR-waves or P-waves.

As described herein, various exemplary systems, methods, and interfacesmay be configured to use electrode apparatus including externalelectrodes, imaging apparatus, display apparatus, and/or computingapparatus to noninvasively assist a user (e.g., a physician) inevaluating pacing therapy, in configuring pacing therapy, in selectingone or more locations (e.g., implantation site regions) proximate apatient's heart for one or more implantable electrodes, and/ornavigating one or more implantable electrodes to one or more selectedlocation(s). An exemplary system 100 including electrode apparatus 110,imaging apparatus 120, display apparatus 130, and computing apparatus140 is depicted in FIG. 4.

The electrode apparatus 110 as shown includes a plurality of electrodesincorporated, or included, within a band wrapped around the chest, ortorso, of a patient 14. The electrode apparatus 110 is operativelycoupled to the computing apparatus 140 (e.g., through one or more wiredelectrical connections, wirelessly, etc.) to provide electrical signalsfrom each of the electrodes to the computing apparatus 140 for analysis.Exemplary electrode apparatus may be described in U.S. ProvisionalPatent Application No. 61/913,759 entitled “Bioelectric Sensor Deviceand Methods” and filed on Dec. 9, 2013 (Docket No. C00006744.USP1(134.0793 0160)), which is incorporated herein by reference in itsentirety. Further, exemplary electrode apparatus 110 will be describedin more detail in reference to FIGS. 5A-5B.

The imaging apparatus 120 may be any type of imaging apparatusconfigured to image, or provide images of, at least a portion of thepatient in a non-invasive manner. For example, the imaging apparatus 120may not use any components or parts that may be located within thepatient to provide images of at least a portion of the patient exceptnon-invasive tools such as contrast solution. It is to be understoodthat the exemplary systems, methods, and interfaces described herein maynoninvasively assist a user (e.g., a physician) in testing whetherpacing therapy stimulates the patient's phrenic nerve, evaluating pacingtherapy, configuring pacing therapy, selecting a location proximate apatient's heart for an implantable electrode, and implanting, ornavigating, an implantable electrode into the patient, e.g., proximatethe patient's heart.

Additionally, the exemplary systems, methods, and interfaces may provideimage guided navigation that may be used to navigate leads includingelectrodes, leadless electrodes, wireless electrodes, catheters, etc.,within the patient's body. Further, although the exemplary systems,methods, and interfaces are described herein with reference to apatient's heart, it is to be understood that the exemplary systems,methods, and interfaces may be applicable to any other portion of thepatient's body.

The imaging apparatus 120 may be configured to capture, or take, x-rayimages (e.g., two dimensional x-ray images, three dimensional x-rayimages, etc.) of the patient 14. The imaging apparatus 120 may beoperatively coupled (e.g., through one or more wired electricalconnections, wirelessly, etc.) to the computing apparatus 140 such thatthe images captured by the imaging apparatus 120 may be transmitted tothe computing apparatus 140. Further, the computing apparatus 140 may beconfigured to control the imaging apparatus 120 to, e.g., configure theimaging apparatus 120 to capture images, change one or more settings ofthe imaging apparatus 120, etc.

It will be recognized that while the imaging apparatus 120 as shown inFIG. 4 may be configured to capture x-ray images, any other alternativeimaging modality may also be used by the exemplary systems, methods, andinterfaces described herein. For example, the imaging apparatus 120 maybe configured to capture images, or image data, using isocentricfluoroscopy, bi-plane fluoroscopy, ultrasound, computed tomography (CT),multi-slice computed tomography (MSCT), magnetic resonance imaging(MRI), high frequency ultrasound (HIFU), optical coherence tomography(OCT), intra-vascular ultrasound (IVUS), two dimensional (2D)ultrasound, three dimensional (3D) ultrasound, four dimensional (4D)ultrasound, intraoperative CT, intraoperative MRI, etc. Further, it isto be understood that the imaging apparatus 120 may be configured tocapture a plurality of consecutive images (e.g., continuously) toprovide video frame data. In other words, a plurality of images takenover time using the imaging apparatus 120 may provide video, or motionpicture, data. Additionally, the images may also be obtained anddisplayed in two, three, or four dimensions. In more advanced forms,four-dimensional surface rendering of the heart or other regions of thebody may also be achieved by incorporating heart data or other softtissue data from an atlas map or from pre-operative image data capturedby MRI, CT, or echocardiography modalities. Image datasets from hybridmodalities, such as positron emission tomography (PET) combined with CT,or single photon emission computer tomography (SPECT) combined with CT,could also provide functional image data superimposed onto anatomicaldata to be used to reach target locations within the heart or otherareas of interest.

The display apparatus 130 and the computing apparatus 140 may beconfigured to display and analyze data such as, e.g., phrenic nervestimulation information (e.g., whether each electrical pacing vectorstimulates the patient's phrenic nerve, what power configuration of eachelectrical pacing vector stimulates the patient's phrenic nerve,electrical activity data with respect to the patient's surfacepotentials after and/or during pacing therapy, etc.), surrogateelectrical activation data, image data, mechanical motion data, etc.gathered, or collected, using the electrode apparatus 110 and theimaging apparatus 120 to noninvasively assist a user inevaluating/configuring pacing therapy and selecting a location forimplantation of an implantable electrode. In at least one embodiment,the computing apparatus 140 may be a server, a personal computer, or atablet computer. The computing apparatus 140 may be configured toreceive input from input apparatus 142 and transmit output to thedisplay apparatus 130. Further, the computing apparatus 140 may includedata storage that may allow for access to processing programs orroutines and/or one or more other types of data, e.g., for driving agraphical user interface configured to noninvasively assist a user.

The computing apparatus 140 may be operatively coupled to the inputapparatus 142 and the display apparatus 130 to, e.g., transmit data toand from each of the input apparatus 142 and the display apparatus 130.For example, the computing apparatus 140 may be electrically coupled toeach of the input apparatus 142 and the display apparatus 130 using,e.g., analog electrical connections, digital electrical connections,wireless connections, bus-based connections, network-based connections,internet-based connections, etc. As described further herein, a user mayprovide input to the input apparatus 142 to manipulate, or modify,information including phrenic nerve stimulation information, one or moregraphical depictions displayed on the display apparatus 130 to viewand/or select one or more target or candidate locations of a portion ofa patient's heart as further described herein.

Although as depicted the input apparatus 142 is a keyboard, it is to beunderstood that the input apparatus 142 may include any apparatuscapable of providing input to the computing apparatus 140 to perform thefunctionality, methods, and/or logic described herein. For example, theinput apparatus 142 may include a mouse, a trackball, a touchscreen(e.g., capacitive touchscreen, a resistive touchscreen, a multi-touchtouchscreen, etc.), etc. Likewise, the display apparatus 130 may includeany apparatus capable of displaying information to a user, such as agraphical user interface 132 including graphical depictions of anatomyof a patient's heart, images of a patient's heart, graphical depictionsof locations of one or more electrodes, graphical depictions of one ormore target or candidate locations, alphanumeric representations of oneor more values, graphical depictions or actual images of implantedelectrodes and/or leads, etc. For example, the display apparatus 130 mayinclude a liquid crystal display, an organic light-emitting diodescreen, a touchscreen, a cathode ray tube display, etc.

The graphical user interfaces 132 displayed by the display apparatus 130may include, or display, one or more regions used to display graphicaldepictions, to display images, to allow selection of one or more regionsor areas of such graphical depictions and images, etc. As used herein, a“region” of a graphical user interface 132 may be defined as a portionof the graphical user interface 132 within which information may bedisplayed or functionality may be performed. Regions may exist withinother regions, which may be displayed separately or simultaneously. Forexample, smaller regions may be located within larger regions, regionsmay be located side-by-side, etc. Additionally, as used herein, an“area” of a graphical user interface 132 may be defined as a portion ofthe graphical user interface 132 located with a region that is smallerthan the region it is located within.

The processing programs or routines stored and/or executed by thecomputing apparatus 140 may include programs or routines forcomputational mathematics, matrix mathematics, decomposition algorithms,compression algorithms (e.g., data compression algorithms), calibrationalgorithms, image construction algorithms, signal processing algorithms(e.g., Fourier transforms, fast Fourier transforms, etc.),standardization algorithms, comparison algorithms, vector mathematics,or any other processing required to implement one or more exemplarymethods and/or processes described herein. Data stored and/or used bythe computing apparatus 140 may include, for example, image data fromthe imaging apparatus 120, electrical signal data from the electrodeapparatus 110, graphics (e.g., graphical elements, icons, buttons,windows, dialogs, pull-down menus, graphic areas, graphic regions, 3Dgraphics, etc.), graphical user interfaces, results from one or moreprocessing programs or routines employed according to the disclosureherein, or any other data that may be necessary for carrying out the oneand/or more processes or methods described herein.

In one or more embodiments, the exemplary systems, methods, andinterfaces may be implemented using one or more computer programsexecuted on programmable computers, such as computers that include, forexample, processing capabilities, data storage (e.g., volatile ornon-volatile memory and/or storage elements), input devices, and outputdevices. Program code and/or logic described herein may be applied toinput data to perform functionality described herein and generatedesired output information. The output information may be applied asinput to one or more other devices and/or methods as described herein oras would be applied in a known fashion.

The one or more programs used to implement the systems, methods, and/orinterfaces described herein may be provided using any programmablelanguage, e.g., a high level procedural and/or object orientatedprogramming language that is suitable for communicating with a computersystem. Any such programs may, for example, be stored on any suitabledevice, e.g., a storage media, that is readable by a general or specialpurpose program running on a computer system (e.g., including processingapparatus) for configuring and operating the computer system when thesuitable device is read for performing the procedures described herein.In other words, at least in one embodiment, the exemplary systems,methods, and/or interfaces may be implemented using a computer readablestorage medium, configured with a computer program, where the storagemedium so configured causes the computer to operate in a specific andpredefined manner to perform functions described herein. Further, in atleast one embodiment, the exemplary systems, methods, and/or interfacesmay be described as being implemented by logic (e.g., object code)encoded in one or more non-transitory media that includes code forexecution and, when executed by a processor, is operable to performoperations such as the methods, processes, and/or functionalitydescribed herein.

The computing apparatus 140 may be, for example, any fixed or mobilecomputer system (e.g., a controller, a microcontroller, a personalcomputer, mini computer, tablet computer, etc.). The exact configurationof the computing apparatus 130 is not limiting, and essentially anydevice capable of providing suitable computing capabilities and controlcapabilities (e.g., graphics processing, etc.) may be used. As describedherein, a digital file may be any medium (e.g., volatile or non-volatilememory, a CD-ROM, a punch card, magnetic recordable tape, etc.)containing digital bits (e.g., encoded in binary, trinary, etc.) thatmay be readable and/or writeable by computing apparatus 140 describedherein. Also, as described herein, a file in user-readable format may beany representation of data (e.g., ASCII text, binary numbers,hexadecimal numbers, decimal numbers, graphically, etc.) presentable onany medium (e.g., paper, a display, etc.) readable and/or understandableby a user.

In view of the above, it will be readily apparent that the functionalityas described in one or more embodiments according to the presentdisclosure may be implemented in any manner as would be known to oneskilled in the art. As such, the computer language, the computer system,or any other software/hardware which is to be used to implement theprocesses described herein shall not be limiting on the scope of thesystems, processes or programs (e.g., the functionality provided by suchsystems, processes or programs) described herein.

FIGS. 5A-5B are conceptual diagrams illustrating exemplary electrodesystems for measuring electrical signals (e.g., body-surface potentialsand, more particularly, torso-surface potentials) from the patient. Theexemplary electrode systems in FIGS. 5A-5B may be configured to measureelectrical signals used to determine whether cardiac pacing isstimulating the patient's phrenic nerve, to measure cardiac improvementinformation during pacing therapy (e.g., pacing therapy that utilizesone or more pacing electrodes to form one or more electrical pacingvectors), etc. As shown in FIG. 5A, the exemplary system 110 includes aset, or array, of electrodes 102, a strap 104, interface/amplifiercircuitry 103, and computing apparatus 140. The electrodes 102 areattached, or coupled, to the strap 104, and the strap 104 may beconfigured to be wrapped around the torso of patient such that theelectrodes 102 surround the patient's torso and/or heart. As furtherillustrated, the electrodes 102 may be positioned around thecircumference of patient, including the posterior, lateral, and anteriorsurfaces of the torso of patient. In other examples, electrodes 102 maybe positioned on any one or more of the posterior, lateral, and anteriorsurfaces of the torso. Further, the electrodes 102 may be electricallyconnected to interface/amplifier circuitry 103 via wired connection 108.The interface/amplifier circuitry 103 may be configured to amplify thesignals from the electrodes 102 and provide the signals to the computingapparatus 140 such as described herein with reference to FIG. 4. Otherexemplary systems may use a wireless connection to transmit the signalssensed by electrodes 102 to the interface/amplifier circuitry 103 and,in turn, the computing apparatus 140, e.g., as channels of data.

Although in the example of FIG. 5A the electrode system 110 includes astrap 104, any of a variety of mechanisms, e.g., tape or adhesives, maybe employed to aid in the spacing and placement of electrodes 102. Insome examples, the strap 104 may include an elastic band, strip of tape,or cloth. In other examples, the electrodes 102 may be placedindividually on the torso of a patient. Further, in other examples,electrodes 102 (e.g., arranged in an array) may be part of, or locatedwithin, patches, vests, and/or other means of securing the electrodes102 to the torso of the patient.

The electrodes 102 may be configured to record, or monitor, theelectrical signals (e.g., depolarizations, repolarizations, etc.)associated with phrenic nerve activity and/or the heart after thesignals have propagated through and/or about the torso of patient. Forexample, the electrodes 102 may be configured to record, or monitor, anyelectrical signals associated non-cardiac tissue such as, e.g., thepatient's diaphragm (e.g., tissues that interact with phrenic nervestimulation), that have propagated through and/or about the torso ofpatient. Each of the electrodes 102 may be used in a unipolarconfiguration to sense the torso-surface potentials. Theinterface/amplifier circuitry 103 may also be coupled to a return orindifferent electrode (not shown) which may be used in combination witheach of electrodes 102 for unipolar sensing. In some examples, about 12electrodes to about 50 electrodes 102 may be spatially distributedaround the torso of patient. Other configurations may have more or fewerelectrodes 102.

The computing apparatus 140 may record and analyze the torso-surfacepotential signals sensed by electrodes 102 and amplified/conditioned bythe interface/amplifier circuitry 103. The computing apparatus 140 maybe configured to analyze the signals from the electrodes 102 todetermine whether pacing therapy is stimulating the patient's phrenicnerve and/or to generate cardiac improvement information (e.g., providedyssynchrony information, dyssynchrony index, etc.) usable to determinewhether pacing electrodes improve cardiac functionality. Additionally,the computing apparatus 140 may be configured to provide output to auser indicative of phrenic nerve stimulation information and/or cardiacimprovement information. Exemplary systems and/or methods may use thephrenic nerve stimulation information and/or cardiac functionalityimprovement information (e.g., dyssynchrony information) to determinewhether one or more electrodes and/or one or more electrical pacingvectors are desirable, optimal, and/or effective for use in pacingtherapy.

In some examples, analysis of electrical signals sensed by the externalelectrodes 102 by the computing apparatus 140 may take intoconsideration the location of electrodes implanted proximate cardiactissue (e.g., electrodes located on leads implanted in the patient'sheart) and/or additional tracking points based on anatomic fiducialelements or intracardiac catheters placed proximate cardiac tissue. Insuch examples, the computing apparatus 140 may be communicativelycoupled to an imaging device 120 as shown in FIG. 4, which may providean image that allows the computing apparatus 140 to determine coordinatelocations of each of the electrodes and/or other anatomic fiducialelements or intracardiac catheters. The imaging device 120 may beconfigured to monitor movement of the one or more visible electrodes toprovide phrenic nerve stimulation information and/or cardiac improvementinformation (e.g., dyssynchrony information).

FIG. 5B illustrates another exemplary electrode system 111 that includesa plurality of electrodes 112 configured to be located about the torsoof the patient and record, or monitor, the electrical signals associatedwith phrenic nerve stimulation and/or the depolarization andrepolarization of the heart after the signals have propagated throughthe torso of patient. The electrode system 110 may include a vest 114upon which the plurality of electrodes is attached, or to which they arecoupled. In at least one embodiment, the plurality, or array, ofelectrodes 112 may be used to provide phrenic nerve stimulationinformation and/or cardiac improvement information (e.g., dyssynchronyinformation). Similar to the electrode system 110, the electrode system111 may include interface/amplifier circuitry 113 electrically coupledto each of the electrodes 112 through a wired connection 118 andconfigured to transmit signals from the electrodes 112 to a computingapparatus 140. As illustrated, the electrodes 112 may be distributedover the torso of patient, including, for example, the anterior,lateral, and posterior surfaces of the torso of patient.

The vest 114 may be formed of fabric, or any other material, with theelectrodes 112 attached thereto. The vest 114 may be configured tomaintain the position and spacing of electrodes 112 on the torso of thepatient. Further, the vest 114 may be marked to assist in determiningthe location of the electrodes 112 on the surface of the torso of thepatient. In some examples, there may be about 25 to about 256 electrodes112 distributed around the torso of the patient, though otherconfigurations may have more or fewer electrodes 112.

The exemplary systems, apparatus, methods, and/or interfaces describedherein are configured to detect phrenic nerve stimulation during pacingtherapy for one or more electrical pacing vectors at one or more powerconfigurations and/or identify one or more optimal electrical pacingvectors for delivering cardiac therapy, and the systems includingelectrodes and computing apparatus described herein with reference toFIGS. 1-5 may utilize the exemplary systems, apparatus, methods, and/orinterfaces. More specifically, the exemplary systems, apparatus,methods, and/or interfaces may be used, for example, to determine whichelectrical vectors (e.g., electrical pacing vectors) defined by one ormore electrodes in the systems of FIGS. 1-5 stimulate the patient'sphrenic nerve, what power configurations used by the electrical vectorsdefined by one or more electrodes in the systems of FIGS. 1-5 stimulatethe patient's phrenic nerve, and/or which electrical vectors defined byone or more electrodes in the systems of FIGS. 1-5 are optimal fordelivering pacing therapy to tissue of the patient.

For example, when the leads 18, 20, 22 of the system 10 of FIGS. 1-3 arelocated, or implanted, in a patient's heart, a plurality of differentelectrical vectors for delivering cardiac therapy may be defined by theelectrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66. As such, theexemplary systems, apparatus, methods, and/or interfaces may be usedwith the system 10 of FIGS. 1-3 to determine which electrodes 40, 42,44, 45, 46, 47, 48, 50, 58, 62, 64, 66 and which electrical vectorsdefined by the electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66may stimulate the patient's phrenic nerve (e.g., a potentiallyundesirable effect) and/or may be optimal for delivering electricaltherapy to the cardiac tissue of the patient.

An exemplary method 150 for identifying one or more optimal electricalpacing vectors is depicted in FIG. 6. The method 150 includes deliveringpacing therapy 152 using a plurality of electrodes in a plurality ofdifferent pacing configurations. The pacing therapy 152 may utilize oneor more electrodes such as the electrodes 40, 42, 44, 45, 46, 47, 48,50, 58, 62, 64, 66 of the system 10. For example, each electrode (e.g.,as a cathode) may be used individually to deliver pacing therapy (e.g.,using the same or a different anode). In other words, one electrode at atime may be used to deliver pacing therapy. Further, for example, morethan one electrode (e.g., two electrodes, three electrodes, etc.) may beused simultaneously to deliver pacing therapy (e.g., if none of theelectrodes used individually achieves capture, if none of the electrodesused individually provides cardiac improvement (e.g., significantcardiac improvement, sufficient cardiac improvement, etc.), etc.). Inother words, more than one electrode at a time may be used to deliverpacing therapy. Additionally, one or more pacing electrodes may deliverelectrical pacing therapy at one or more different power configurations.For example, the one or more pacing electrodes may be configured todeliver more than one pacing pulse (e.g., each pacing pulse having aselected pacing width, each pacing pulse separated by a selectedseparation time period, etc.), deliver pacing pulses at greatervoltages, deliver longer pacing pulses (e.g., pacing pulses have alonger time duration or pulse width, etc.), etc. Further, the powerconfigurations of a pacing vector may be re-configured (e.g., the powerof the electrical stimulation may be increased by increasing the numberof pulses, the width of the pulses, and/or the voltage of the pulsesuntil the pacing vector achieves capture (e.g., trigger depolarizationof cardiac tissue).

In essence, the exemplary method 150 may deliver pacing therapy using aplurality of different pacing configurations (e.g., a plurality ofdifferent pacing vectors at a plurality of different powerconfigurations) using the plurality of electrodes. In some embodiments,a common anode may be used for each different pacing configuration. Inother embodiments, each different pacing configuration may use adifferent anode.

For each different pacing configuration, the method 150 may generatecardiac improvement information 154. The cardiac improvement informationmay be defined as information that is representative of a change inmechanical and/or electrical cardiac functionality resulting frompacing. In other words, the cardiac improvement information may beindicative of improvement of cardiac functionality from baseline cardiacfunctionality. The baseline cardiac functionality may be cardiacfunctionality without any pacing therapy being delivered to the patient.

In one or more embodiments, the cardiac improvement information mayinclude dyssynchrony information. Dyssynchrony information may bedefined as information indicative of the mechanical and/or electricaldyssynchrony of the heart. In at least one embodiment, the dyssynchronyinformation may include a standard deviation of ventricular activationtimes corresponding to electrodes on the surface array. Further,regional dyssynchrony may be also computed from the standard deviationof activation times corresponding to electrodes located in certainanatomic areas of the torso, for e.g. electrodes on the left side of thetorso would be used to compute regional LV dyssynchrony. Thedyssynchrony information may be generated using one or more varioussystems and/or methods. Dyssynchrony information may be generated usingan array, or a plurality, of surface electrodes and/or imaging systemsas described in U.S. Pat. App. Pub. No. 2012/0283587 A1 published Nov.8, 2012 and entitled “ASSESSING INRA-CARDIAC ACTIVATION PATTERNS ANDELECTRICAL DYSSYNCHRONY,” U.S. Pat. App. Pub. No. 2012/0284003 A1published Nov. 8, 2012 and entitled “ASSESSING INTRA-CARDIAC ACTIVATIONPATTERNS”, and U.S. Pat. No. 8,180,428 B2 issued May 15, 2012 andentitled “METHODS AND SYSTEMS FOR USE IN SELECTING CARDIAC PACINGSITES,” each of which is incorporated herein by reference in itsentirety.

Dyssynchrony information may include one or more dyssynchrony indices.For example, one of the indices of electrical dyssynchrony may be astandard deviation index computed as the standard deviation of theactivations-times (SDAT) of some or all of the electrodes on the surfaceof the torso of patient. In some examples, the SDAT may be calculatedusing the estimated cardiac activation times over the surface of a modelheart.

A second example index of dyssynchrony may be a range of activationtimes (RAT) which may be computed as the difference between the maximumand the minimum torso-surface or cardiac activation times, e.g.,overall, or for a region. The RAT reflects the span of activation timeswhile the SDAT gives an estimate of the dispersion of the activationtimes from a mean. The SDAT also provides an estimate of theheterogeneity of the activation times, because if activation times arespatially heterogeneous, the individual activation times will be furtheraway from the mean activation time, indicating that one or more regionsof heart have been delayed in activation. In some examples, the RAT maybe calculated using the estimated cardiac activation times over thesurface of a model heart.

A third example index of electrical dyssynchrony estimates thepercentage of surface electrodes located within a particular region ofinterest for the torso or heart, whose associated activation times aregreater than a certain percentile, for example the 70th percentile, ofmeasured QRS complex duration or the determined activation times forsurface electrodes. The region of interest may be a posterior, leftanterior, and/or left-ventricular region, as examples. This index, thepercentage of late activation (PLAT), provides an estimate of percentageof the region of interest, e.g., posterior and left-anterior areaassociated with the left ventricular area of heart, which activateslate. A large value for PLAT may imply delayed activation of asubstantial portion of the region, e.g., the left ventricle, and thepotential benefit of electrical resynchronization through CRT bypre-exciting the late region, e.g., of left ventricle. In otherexamples, the PLAT may be determined for other subsets of electrodes inother regions, such as a right anterior region to evaluate delayedactivation in the right ventricle. Furthermore, in some examples, thePLAT may be calculated using the estimated cardiac activation times overthe surface of a model heart for either the whole heart or for aparticular region, e.g., left or right ventricle, of the heart.

In one or more embodiments, the cardiac improvement information mayinclude indicators of favorable changes in global cardiac electricalactivation such as, e.g., described in Sweeney et al., “Analysis ofVentricular Activation Using Surface Electrocardiography to Predict LeftVentricular Reverse Volumetric Remodeling During CardiacResynchronization Therapy,” Circulation, 2010 February 9, 121(5): 626-34and/or Van Deursen, et al., “Vectorcardiography as a Tool for EasyOptimization of Cardiac Resynchronization Therapy in Canine LBBBHearts,” Circulation Arrhythmia and Electrophysiology, 2012 June 1,5(3): 544-52, each of which is incorporated herein by reference in itsentirety. Cardiac improvement information may also include measurementsof improved cardiac mechanical function measured by imaging or othersystems to track motion from implanted leads within the heart as, e.g.,described in Ryu et al., “Simultaneous Electrical and Mechanical MappingUsing 3D Cardiac Mapping System: Novel Approach for Optimal CardiacResynchronization Therapy,” Journal of Cardiovascular Electrophysiology,2010 February, 21(2): 219-22, Sperzel et al., “IntraoperativeCharacterization of Interventricular Mechanical Dyssynchrony UsingElectroanatomic Mapping System—A Feasibility Study,” Journal ofInterventional Cardiac Electrophysiology, 2012 November, 35(2): 189-96,and/or U.S. Pat. App. Pub. No. 2009/0099619 A1 entitled “METHOD FOROPTIMIZING CRT THERAPY” and published on Apr. 16, 2009, each of which isincorporated herein by reference in its entirety.

In one or more embodiments, the cardiac improvement information may begenerated by tracking lead motion and inter-electrode distances withfluoroscopy to generate at least one metric (e.g., value(s), functions,comparisons, differences, averages, slopes, etc.) that correlates withcardiac contractility. For example, a contractility curve may begenerated based on the variation in distance between the RV and LVelectrode-tips during the course of one or more cardiac cycles and oneor more metrics relating to fractional shortening may be derived fromthis curve. In another embodiment, multiple points on intracardiac leadsand/or catheter systems may be tracked during course of one or morecardiac cycles to generate metrics relating to contractility or globalcardiac mechanical dyssynchrony.

In at least one embodiment, a computing apparatus such as the computingapparatus 140 described herein with reference to FIG. 4 may be used tomeasure a dyssynchrony index during intrinsic rhythm and during pacingwith each electrode to generate cardiac functionality information usedto select one or more electrodes to be possibly used in one or moreoptimal pacing vectors. For example, a physician may place a LV lead ina target location and a user may initiate CRT pacing from theprogrammer/analyzer. For each of a plurality of CRT pacingconfigurations, the system may be configured to detect the pacingparameters displayed on the programmer/analyzer screen (e.g., usingcharacter recognition from VGA output), and then, the system may measurea dyssynchrony index. The CRT pacing configurations may beautomatically, or manually, changed on a programmer/analyzer. Then, thesystem may classify each of the electrodes, or electrode configurations,as one of “improved,” “neutral,” or “worsened” using the dyssynchronymeasurements.

In at least one embodiment, changes in dyssynchrony during CRT pacingmay be measured from each LV electrode as the cathode at a common A-Vdelay (e.g., less than 60 milliseconds from the intrinsic AV time) to,e.g., avoid fusion of the pacing depolarization with the intrinsicdepolarization. Further, a common anode may be selected for thesepreliminary evaluations such as, e.g., a RV coil. Cathode capture can beverified by morphology of a LV cathode to RV coil electrocardiogram.

In at least one embodiment, if poor dyssynchrony is measured, theexemplary method may switch to higher amplitudes to encourage someanodal capture and/or switch to multi-site pacing (e.g., pacing usingmore than one electrode) to, e.g., see if dyssynchrony improves.

Based on the cardiac improvement information, the method 150 may selectone or more electrodes 156. To select the one or more electrodes, thecardiac improvement information may provide one or more numericalmetrics or values (e.g., value(s), functions, differences, comparisons,averages, slopes, etc.) that may be compared against each other and/orone or more threshold values. The electrodes having the best cardiacimprovement information and/or metrics or values exceeding selectedthresholds may be selected to be used in, or defining, one or more(e.g., one, two or more, a plurality, etc.) different pacing vectors.

For example, dyssynchrony information may include a dyssynchronyimprovement value for each electrode. The dyssynchrony improvement valuemay be generated by monitoring the dyssynchrony of the patient's heartwithout resynchronization pacing therapy to establish a baseline,monitoring the dyssynchrony of the patient's heart during pacing usingeach electrode (or electrode configuration), and comparing the baselinedyssynchrony to the dyssynchrony during resynchronization pacing toprovide a dyssynchrony improvement value for each electrode (orelectrode configuration). In at least one embodiment, the dyssynchronyimprovement value for each electrode (or electrode configuration) may becompared to a threshold value and each electrode (or electrodeconfiguration) exceeding the threshold value may be selected.

The dyssynchrony improvement values themselves may assist in defining,or selecting the threshold value. Generally, the threshold may bedefined as a decreasing function of the maximal dyssynchrony improvementvalue (e.g., maximal relative improvement in resynchronization). Morespecifically, the threshold value may be calculated by multiplying afactor by the maximal, or maximum, dyssynchrony improvement value.

Further, the factor used to calculate the threshold value may beselected based on the maximum generated dyssynchrony improvement value.In at least one embodiment, if a maximal dyssynchrony improvement value,or maximal relative improvement in resynchronization value, is between0% and 5%, then the factor may be set of 0.9. If the maximaldyssynchrony improvement value is between 5% and 10%, then the factormay be set to 0.8. If the maximal dyssynchrony improvement value isbetween 10% and 25%, then the factor may be set to 0.75. If the maximaldyssynchrony improvement value is above 25%, then the factor may be setto 0.7. A threshold for a maximal dyssynchrony improvement value meansthat all electrodes with a resynchronization efficacy greater than thethreshold multiplied by the maximal dyssynchrony improvement valueshould be selected (e.g., selected to be possibly used in one or moreoptimal pacing vectors).

The one or more electrodes selected based on the cardiac improvementinformation 156 may define, or be used to form, one or more electricalvectors configured to deliver therapy to the patient's heart. Forexample, if a first left ventricular electrode and a second leftventricular electrode are selected based on the cardiac improvementinformation, one or more electrical vectors may be defined between thefirst left ventricular electrode and one or all of the remainingelectrodes and one or more electrical vectors may be defined between thesecond left ventricular electrode and one or all of the remainingelectrodes.

In other words, the selection of one or more electrodes based on thecardiac improvement information 156 may provide one or more electricalvectors that may be used to deliver therapy. To determine whether theone or more electrical vectors are optimal, the method 150 may take intoconsideration information such as longevity information for eachelectrical vector 158, phrenic nerve stimulation information such asdescribed herein with respect to FIGS. 14-19, etc.

For example, generated longevity information 158 may include an energyexpenditure value for each electrical vector, which can be determinedbased on a capture threshold for each electrical vector, an impedancevalue for each electrical vector, a pulse width for each electricalvector (e.g., required for capture), information regarding each pacingpulse for multi-site pacing configurations, etc. Energy expenditure maybe expressed in actual or relative estimated energy usage or actual orrelative predicted battery longevity when an IMD operates using aparticular parameter selection.

One or more processes and/or methods disclosed in U.S. Pat. App. Pub.No. 2012/0101543 A1 filed on Oct. 21, 2010 and entitled “CAPTURETHRESHOLD MEASUREMENT FOR SELECTION OF PACING VECTOR,” U.S. Pat. App.Pub. No. 2012/0101546 A1 filed on Jul. 29, 2011 and entitled “METHOD ANDAPPARATUS TO DETERMINE THE RELATIVE ENERGY EXPENDITURE FOR A PLURALITYOF PACING VECTORS,” U.S. Pat. App. Pub. No. 2013/0030491 A1 filed onJul. 28, 2011 and entitled “METHOD FOR DISCRIMINATING ANODAL ANDCATHODAL CAPTURE,” and U.S. patent application Ser. No. 13/790,683 filedon Mar. 8, 2013 and entitled “CAPTURE THRESHOLD MEASUREMENT FORSELECTION OF PACING VECTOR” (Attorney Docket No.: C00002602.USU2), eachof which is incorporated herein by reference in their entirety, may beimplemented to provide cardiac improvement information such as longevityinformation, capture thresholds, impedance, etc. for one or moreselected electrical vectors.

After longevity information has been generated for each electricalvector 158, the method 150 may identify one or more optimal electricalvectors based on the longevity information 160. For example, the method150 may identify the optimal electrical vectors and automaticallyconfigure the pacing system to use the optimal electrical vectors forpacing. Further, for example, the method 150 may generate a graphicaluser interface 132 depicting each of the selected electrical vectors andtheir associated longevity information, e.g., as shown in FIG. 11.Further, the method 150 may identify the selected electrical vectorshaving optimal longevity information on the graphical user interface132, e.g., by highlighting, circles, arrows, etc. (e.g., as shown inFIG. 9).

In one or more embodiments, the method 150 may identify the most optimalelectrical vector, e.g., by identifying the electrical vector having oneor more of the greatest longevity, lowest capture threshold, smallestimpedance, etc.

Additionally, whether the one or more selected electrical vectorsstimulate the phrenic nerve may be used to identify the one or moreoptimal electrical vectors. For example, the method 150 may includedetermining whether each electrical vector stimulates the phrenic nerveand identifying the optimal electrical vector of the plurality ofelectrical vectors based on an absence of phrenic nerve stimulation.

After the method 150 has identified one or more optimal electricalvectors based on the longevity information 160, the method 150 mayfurther 162 allow a user (e.g., physician) to navigate, or locate, oneor more electrodes 162 (e.g., implantable electrodes on one or moreleads, wireless/leadless electrodes, etc.) to one or more regionsproximate a patient's heart to provide pacing therapy, e.g., using theone or more identified optimal electrical vectors 160. For example, agraphical user interface 132, such as shown in FIG. 11 described furtherherein, may include a graphical depiction and/or actual imaging (e.g.,using imaging apparatus 120 of FIG. 4) of a patient's heart inconjunction with the identified one or more optimal pacing vectors.Using the graphical user interface 132, a user may navigate, or locate,the one or more electrodes in the desired locations based on theidentified optimal electrical vectors 160.

Exemplary systems, methods, apparatus, and interfaces for electrodelocation selection and implantation may be described in U.S. patentapplication Ser. No. 13/916,353 filed on Jun. 12, 2013 and entitled“Implantable Electrode Location Selection,” U.S. patent application Ser.No. 13/916,377 filed on Jun. 12, 2013 and entitled “ImplantableElectrode Location Selection,” U.S. Provisional Patent Application No.61/817,483 filed on Apr. 30, 2013 and entitled “Identifying EffectiveElectrodes,” and U.S. Provisional Patent Application No. 61/913,795filed on Dec. 9, 2013 and entitled “Systems, Methods, and Interfaces forIdentifying Effective Electrodes,” each of which is incorporated hereinby reference in its entirety.

Exemplary graphical user interfaces 132 including displays and tablesused and/or generated by the exemplary methods and/or systems describedherein for identifying one or more optimal electrical vectors are shownin FIGS. 7-11. As shown in FIG. 7, cardiac improvement information hasbeen generated for four different left ventricular electrodes (LV1, LV2,LV3, LV4). Since the maximal improvement is 5% in this example, thefactor for generating the threshold value may be set to 0.9 so allelectrodes with relative improvement greater than or equal to 0.9multiplied by 5% (i.e., the maximal improvement) may be consideredequivalent/effective, and thus, may be considered as the cathode foroptimal vector selection. In this example, only LV1 has a relativeimprovement greater than or equal to 4.5. For lower relativeimprovements (e.g., 0% to 5%) as depicted in FIG. 6, the factor forgenerating the threshold for equivalence should be high (e.g., 0.9).

As shown in the exemplary graphical user interface 132 of FIG. 8,cardiac improvement information has been again generated for fourdifferent left ventricular electrodes (LV1, LV2, LV3, LV4). Sincemaximal improvement is 40%, the factor for generating the threshold maybe set to 0.7 so all electrodes with relative improvement greater thanor equal to 0.7 multiplied by 40% (i.e., the maximal improvement) may beconsidered equivalent/effective, and thus, may be considered as thecathode for optimal vector selection. In this exemplary, two electrodes,LV2 and LV3, have a relative improvement greater than or equal to 28%.For larger improvements (e.g., greater than 28%) as depicted in FIG. 7,the factor for generating the threshold for equivalence can be morerelaxed (e.g., 0.7).

Longevity information may be generated for all possible vectors with theselected electrodes, LV2 and LV3, of FIG. 7 as cathodes, and may bepresented in the exemplary graphical interface 132 depicting a table asshown in FIG. 9. As shown, vectors LV2-LV3 and LV2-LV4 are indicated ashaving maximum relative longevity. Additionally, phrenic nervestimulation information is depicted in the table of FIG. 9.

Vector LV2-LV3 may be determined as being the most optimal vector basedon the longevity information and the phrenic nerve stimulationinformation (e.g., such as phrenic nerve stimulation being absent). Asshown in FIG. 9, an indication 172 (i.e., an oval) may be depicted on agraphical user interface used to select electrical vectors to indicatethe most optimal electrical vector.

Although not shown, all vectors corresponding to the chosen LV cathodesand which do not have associated phrenic nerve stimulation may be sortedin descending order of longevity (e.g., max longevity at the top) tomake the selection convenient. In this example, the system mayautomatically select or the implanter or physician may select LV2-LV3 asthe pacing vector to be used for pacing therapy.

An exemplary graphical user interface 132 depicting a table of longevityinformation, phrenic nerve stimulation information, and cardiacimprovement information for a plurality of electrical vectors is shownin FIG. 10. In this example, the cardiac improvement information isdisplayed simultaneously with the longevity information and phrenicnerve stimulation information. As shown, the LV3-LV4 vector may beidentified as being the most optimal electrical vector because, e.g.,electrode LV3 provided a change in dyssynchrony index of −10% (e.g., animprovement of 10%) and the relative longevity has been determined to be9 months less than a maximum longevity. Although the dyssynchrony indexis indicated as a negative value (i.e., −10%) when indicating animprovement and a positive value when indicating a worsened condition,it to be understood that the dyssynchrony index may be indicated aspositive value when indicating an improvement and a negative value whenindicating a worsened condition.

An exemplary graphical user interface 132 including a graphicalrepresentation of a pair of leads, a LV lead and a RV lead, is depictedin FIG. 11, which define the electrode vectors shown and described withrespect to FIG. 10. Although not shown, the graphical user interface ofFIG. 11 may further include the table of FIG. 10, e.g., to displayinformation to a physician, to allow a physician to select one or moreoptimal vectors, to identify the one or more optimal vectorsgraphically, etc. As shown, cardiac improvement information andlongevity information are depicted proximate the electrical vectorsdefined by the electrodes of the leads.

Generally, any factor (e.g., cardiac improvement information, longevityinformation, phrenic nerve stimulation information, etc.) alone or incombination may be used to identify one or more optimal electricalvectors. For example, dyssynchrony information may be used incombination with phrenic nerve stimulation information, dyssynchronyinformation may be used in combination with longevity information,longevity information may be used alone, dyssynchrony information may beused alone, phrenic nerve stimulation may be used alone, etc.

The graphical user interfaces 132 described herein with reference toFIGS. 7-11 may be provided to users such as physicians to assist them indetermining which of the electrical vectors to use for pacing therapy(e.g., such as before implantation of pacing electrodes, duringimplantation of pacing electrodes, or in follow-up visits afterimplantation of pacing electrodes) and/or navigating one or moreelectrodes (e.g., implantable electrodes on one or more leads) to one ormore regions of a patient's heart to perform pacing at one or moreelectrical vectors.

An exemplary graphical user interface 132 including blood vessel anatomy134 of a patient's heart is shown in FIG. 12 that may be used by a userto navigate an implantable electrode to a region of the patient's heart.The blood vessel anatomy as well as other data such as mechanical motioninformation, etc. of the heart may be captured using the imagingapparatus 120 described herein, which may be configured to image atleast a portion of blood vessel anatomy of the patient's heart andprovide image data used by the computing apparatus 140 to providemechanical motion information or data. The data or information depictedon the blood vessel anatomy of the patient's heart in FIG. 12 may befurther monitored, or gathered, using the electrode apparatus 110described herein.

A user may view and/or use the graphical user interface 132 of FIG. 12to determine, or identify, one or more candidate site regions of thedisplayed portion or region of the patient's heart for implantation ofimplantable electrodes. For example, a user may view mechanical motioninformation, e.g., grey-scaling or color-coding applied to the bloodvessel anatomy in FIG. 12, and identify a candidate site region of thepatient's heart based on the mechanical motion information. For example,a user may identify one or more regions having, e.g., mechanical motiontimes greater than a threshold, having the longest mechanical motiontime, etc.

Another exemplary graphical user interface 132 including a graphicaldepiction of a patient's heart 12 is shown in FIG. 13 that may be usedby a user to navigate an implantable electrode to a region of thepatient's heart. More specifically, a posterior side of a human heart 12is depicted in the graphical user interface 132 of FIG. 13 withsurrogate electrical activation times 136 color-coded, or gray-scaled,across the surface of the heart 12. As used herein, surrogate electricalactivation data (e.g., surrogate electrical activation times, surrogateelectrical activation time maps, etc.) may be defined as datarepresentative of actual, or local, electrical activation data of one ormore regions of the patient's heart. For example, electrical signalsmeasured at the left anterior surface location of a patient's torso maybe representative, or surrogates, of electrical signals of the leftanterior left ventricle region of the patient's heart, electricalsignals measured at the left lateral surface location of a patient'storso may be representative, or surrogates, of electrical signals of theleft lateral left ventricle region of the patient's heart, electricalsignals measured at the left posterolateral surface location of apatient's torso may be representative, or surrogates, of electricalsignals of the posterolateral left ventricle region of the patient'sheart, and electrical signals measured at the posterior surface locationof a patient's torso may be representative, or surrogates, of electricalsignals of the posterior left ventricle region of the patient's heart.

As shown, the posterolateral left ventricle region shows late activation(e.g., about 150 milliseconds). In other embodiments, both a posteriorand anterior side of a human heart may be graphically depicted andoverlaid with electrical activation information. The data or informationdepicted on the patient's heart 12 in FIG. 13 may be further monitored,or gathered, using the electrode apparatus 110 described herein.

As described herein, the exemplary systems, methods, and interfaces mayprovide phrenic nerve stimulation information for one or more electricalpacing vectors at one or more power configurations. An exemplary method200 for detecting phrenic nerve stimulation during pacing therapy isdepicted in FIG. 14. The method 200 includes delivering pacing therapyusing one or more electrical pacing vectors at one or more powerconfigurations 202. As shown in FIG. 14, process 202 is written asdelivering pacing therapy using nth electrical vector at mth powerconfiguration, where n and m may each represent one or more or aplurality. For example, each of n electrical pacing vectors at mdifferent power configurations may be used in process 202 to deliverpacing therapy. In one or more embodiments, the pacing therapy may bedelivered at a short atrioventricular delay such as, e.g., less than orequal to about 50 milliseconds, to avoid interference of pacing withintrinsic electrical conduction (e.g., if the patient has intrinsicatrio-ventricular electrical conduction).

Each electrical pacing vector may utilize one or more electrodes such asthe electrodes 40, 42, 44, 45, 46, 47, 48, 50, 58, 62, 64, 66 of thesystem 10. For example, each electrode may be used individually todeliver pacing therapy. In other words, one electrode at a time may beused to deliver pacing therapy. Further, for example, more than oneelectrode (e.g., two electrodes, three electrodes, etc.) may be usedsimultaneously to deliver pacing therapy if, e.g., none of theelectrodes used individually achieves capture, if none of the electrodesused individually provides cardiac improvement (e.g., significantcardiac improvement, sufficient cardiac improvement, etc.), etc. Inother words, more than one electrode at a time may be used to deliverpacing therapy. Additionally, one or more pacing electrodes may deliverelectrical pacing therapy at one or more different power configurations.For example, the one or more pacing electrodes may be configured todeliver more than one pacing pulse (e.g., each pacing pulse having aselected pacing width, each pacing pulse separated by a selectedseparation time period, etc.), deliver pacing pulses at greatervoltages, deliver longer pacing pulses (e.g., pacing pulses have alonger time duration or pulse width, etc.), etc. Further, the powerconfigurations of a pacing vector may be re-configured (e.g., the powerof the electrical stimulation may be increased by increasing the numberof pulses, the width of the pulses, and/or the voltage of the pulses)until the pacing vector achieves capture (e.g., trigger depolarizationof cardiac tissue).

For each different electrical pacing vector and power configuration, themethod 200 may monitor electrical activity of the patient (e.g., surfacepotentials, depolarizations, repolarizations, etc.) using externalelectrodes 204 such as the external electrodes of electrode apparatus110, 112. The method 200 may include monitoring electrical activity ofthe patient 204 using one or more external electrodes, a set of externalelectrodes proximate a selected location of the torso of the patient,and/or all of the external electrodes. In at least one embodiment, themethod 200 may monitor the electrical activity of the patient 204 usinga set of electrodes located proximate the lower, anterior side of thetorso of the patient.

The method 200 may further monitor a selected, or predetermined,portion, or time window, of the electrical activity of the patient usingexternal electrodes 204. For example, the method 200 may monitorelectrical signals using the external electrodes 204 for a time periodafter the delivery of pacing therapy (e.g., one or more pacing pulsesused to depolarize cardiac tissue) that is greater than or equal toabout 5 milliseconds (ms), greater than or equal to about 7 ms, greaterthan or equal to about 10 ms, greater than or equal to about 12 ms,greater than or equal to about 15 ms, greater than or equal to about 20ms, greater than or equal to about 30 ms, greater than or equal to about50 ms, greater than or equal to about 75 ms, etc. Further, for example,the method 200 may monitor electrical signals using the externalelectrodes 204 for a time period after the delivery of pacing therapy(e.g., one or more pacing pulses to depolarize cardiac tissue) that isless than or equal to about 500 ms, less than or equal to about 300 ms,less than or equal to about 250 ms, less than or equal to about 200 ms,less than or equal to about 150 ms, less than or equal to about 100 ms,less than or equal to about 80 ms, less than or equal to about 60 ms,less than or equal to about 50 ms, less than or equal to about 40 ms,less than or equal to about 35 ms, less than or equal to about 30 ms,etc. The electrical activity monitored for a time period after thedelivery of pacing therapy may be described as a “window” of theelectrical activity of the patient.

Additionally, the exemplary method 200 may monitor electrical signalsusing the external electrodes 204 for multiple time windows over aplurality of cardiac cycles. One or more statistical operations (e.g.,averaging, etc.) may be performed on the plurality of time-windowedsignals to provide a composite signal.

The delivering of pacing therapy 202 and the monitoring of electricalsignals 204 for use in phrenic nerve stimulation detection may beperformed while the patient is in a resting position or posture such as,e.g., supine, lying on right side, lying on left side, sitting, standingup, etc.

The method 200 may then determine whether the patient's phrenic nervehas been stimulated 206 by the pacing therapy based on the monitoredelectrical activity. For example, the amplitude of the monitoredelectrical activity may be greater when the patient's phrenic nerve isstimulated by pacing therapy than when the patient's phrenic nerve isnot stimulated by pacing therapy.

A graph of electrical signals monitored over time by multiple externalelectrodes coupled to a patient that is not undergoing phrenic nervestimulation is shown in FIG. 15. Each line represents the electricalactivity for a different external electrode after the delivery of pacingtherapy. As shown, most of the electrical activity does not exceed 10millivolts (mV), which may indicate that patient's phrenic nerve is notstimulated.

A graph of electrical signals monitored over time by multiple externalelectrodes coupled to a patient that is undergoing phrenic nervestimulation is shown in FIG. 16. Each line represents the electricalactivity for a different external electrode after the delivery of pacingtherapy. As shown, a portion of the electrical activity does exceed 10millivolts (mV), which may indicate that patient's phrenic nerve isstimulated. More specifically, 10 lines representing electrical activitymonitored by different electrodes exceed 10 mV.

To determine whether the patient's phrenic nerve has been stimulated 206by the pacing therapy based on the monitored electrical activity, themethod 200 may use one or more mathematical and/or statisticaltechniques and processes such as, e.g., comparisons, averages,thresholds, baseline values, proportions, ratios, normalizationprocesses, etc. For example, in one embodiment, the method 200 maydetermine whether the patient's phrenic nerve is stimulated by thepacing therapy by comparing a maximum peak-to-peak amplitude of themonitored electrical activity to a threshold value. If the maximumpeak-to-peak amplitude of the electrical activity monitored by anexternal electrode is greater than the threshold value, then theelectrical activity monitored by that external electrode may indicatethat the patient's phrenic nerve has been stimulated by the pacingtherapy.

The threshold value may be greater than or equal to about 5 mV, greaterthan or equal to about 7 mV, greater than or equal to about 10 mV,greater than or equal to about 15 mV, greater than or equal to about 20mV, greater than or equal to about 25 mV, greater than or equal to about30 mV, greater than or equal to about 35 mV, greater than or equal toabout 40 mV, greater than or equal to about 50 mV, etc. Further, thethreshold value may be less than or equal to about 100 mV, less than orequal to about 80 mV, less than or equal to about 60 mV, less than orequal to about 50 mV, less than or equal to about 40 mV, less than orequal to about 30 mV, less than or equal to about 25 mV, less than orequal to about 15 mV, etc.

Further, the threshold value may be normalized to the monitoredelectrical activity. For example, the threshold value may be a multipleof a baseline value (e.g., twice the baseline value, three times thebaseline value, four times the baseline value, five times the baselinevalue, etc.). The baseline value may be established using one or moreprocesses or techniques. For example, baseline electrical value may beestablished by monitoring electrical activity during atrial-only pacing(e.g., so as to avoid inadvertently stimulating the phrenic nerve) orduring intrinsic rhythm. Further, for example, a baseline electricalvalue may be established by monitoring electrical activity usingexternal electrodes located on the posterior side of the patient'storso.

The determination of whether the patient's phrenic nerve has beenstimulated 206 by the pacing therapy may utilize each of a plurality ofelectrical signals monitored by a plurality of external electrodes to,e.g., avoid outliers, artifacts, errors, electrode contact issues, etc.For example, a plurality of electrical signals may be monitored by aplurality of external electrodes, and the method 200 may determine thatthe patient's phrenic nerve has been stimulated 206 by the pacingtherapy if a selected percentage, or proportion, of the plurality ofelectrical signals exceeds a threshold value. The selected percentagemay be greater than or equal to about 20%, greater than or equal toabout 25%, greater than or equal to about 30%, greater than or equal toabout 35%, greater than or equal to about 40%, greater than or equal toabout 50%, greater than or equal to about 60%, greater than or equal toabout 70%, greater than or equal to about 75%, greater than or equal toabout 80%, greater than or equal to about 85%, etc., and/or less than orequal to about 90%, less than or equal to about 80%, less than or equalto about 70%, less than or equal to about 60%, less than or equal toabout 55%, less than or equal to about 50%, less than or equal to about45%, less than or equal to about 40%, less than or equal to about 35%,etc.

Additionally, as described herein, only a portion of external electrodesof a plurality of external electrodes (e.g., on a vest as shown in FIG.5B) may be used to monitor electrical activity for use in determiningwhether the patient's phrenic nerve has been stimulated. For example,only the external electrodes located on the anterior side of the torsoof the patient may be used to determine whether the patient's phrenicnerve has been stimulated. Further, for example, only a selected set ofthe external electrodes located on the anterior side of the torso of thepatient may be used to determine whether the patient's phrenic nerve hasbeen stimulated. Further, for example, only a set of the externalelectrodes located on the lower, anterior side of the torso of thepatient may be used to determine whether the patient's phrenic nerve hasbeen stimulated.

After the method 200 has determined whether the patient's phrenic nervehas been stimulated 206 for a particular electrical pacing vector andpower configuration, the method 200 may loop back to the beginning todeliver pacing therapy 202 if more power configurations of m powerconfigurations have not been tested for the electrical pacing vector orif more electrical pacing vectors of n electrical pacing vectors havenot been tested 208. The method 200 may continue until each electricalpacing vector n and power configuration m has been tested for phrenicnerve stimulation.

The method 200 may further include displaying phrenic nerve stimulationinformation 210 with respect to the electrical pacing vectors and powerconfigurations tested for phrenic nerve stimulation. For example, asshown in the graphical user interface 132 of FIG. 9, an indication ofeither “Absent” or “Present” for phrenic nerve stimulation is displayedfor each electrical pacing vector, which may assist a user inconfiguring, evaluating, and/or selecting an electrical pacing vectorfor delivery of pacing therapy to the patient. In one or moreembodiments, an indication 172 may also be displayed indicating theoptimal electrical pacing vector. As shown, the indicated optical pacingvector is indicated as not stimulating the patient's phrenic nerve.Further, further example, as shown in the graphical user interface 132of FIG. 10, an indication of either “Yes,” “No,” or “Not Tested” forphrenic nerve stimulation is displayed for each electrical pacingvector. In at least one embodiment, an additional category may bedisplayed on the graphical user interface 13 that indicates that whilePNS may exists for a particular electrical pacing vector, the PNS existsat a power configuration/level that is considerably higher than would beused clinically.

Additionally, the phrenic nerve stimulation information may include eachpower configuration for each electrical pacing vector such that, e.g., auser may be able to see, or read, phrenic nerve stimulation informationfor each of the power configurations. In another example, only thelowest power configuration for each electrical vector that exhibitsphrenic nerve stimulation may be included in the phrenic nervestimulation information.

Graphical representations of electrical activity monitored on a patientusing three different electrical pacing vectors, or pacing sites (e.g.,AIV mid, AIV basal, mid-lateral basal), are shown in FIG. 17.Specifically, the maximum peak-to-peak amplitudes of the electricalactivity monitored by the electrodes on the anterior and posterior sidesof the patient's torso are color coded spatially about graphicalrepresentations of the patient's anterior and posterior torso. Asdepicted, none, or not a significant portion, of the electrical activitymonitored on the anterior side of the patient's torso during pacingtherapy for each of these three electrical pacing vectors exceeds athreshold value of 20 mV. Thus, the electrical activity depicted in FIG.17 does not indicate phrenic nerve stimulation for any of the threedifferent electrical pacing vectors.

Graphical representations of electrical activity monitored on a patientusing two different electrical pacing vectors, or pacing sites (e.g.,postero-lateral apical, postero-lateral mid), are shown in FIG. 18.Specifically, the maximum peak-to-peak amplitudes of the electricalactivity monitored by the electrodes on the anterior and posterior sidesof the patient's torso are color coded spatially about graphicalrepresentations of the patient's anterior and posterior torso. Asdepicted, a significant portion of the electrical activity monitored onthe anterior side of the patient's torso during pacing therapy for eachof these two electrical pacing vectors exceeds a threshold value of 20mV. Thus, the electrical activity depicted in FIG. 18 does indicatephrenic nerve stimulation for each of the two different electricalpacing vectors.

As described herein, the electrical activity monitored by externalelectrodes for use in determining whether the patient's phrenic nerve isstimulated by pacing therapy may be normalized. Graphicalrepresentations of electrical activity monitored on a patient using twodifferent biventricular electrical pacing vectors, or pacing sites(e.g., Site 1, Site 2), are shown in FIG. 19. The electrical activityhas been normalized to a scale of 1-5. In this case, the normalizationis performed by dividing the peak-to-peak amplitude of the windoweddepolarization complex at each electrode with the minimum peak-to-peakamplitude among all electrodes. As depicted, a significant portion ofthe electrical activity monitored on the anterior side of the patient'storso during pacing therapy for Site 1 meets or exceeds a normalizedthreshold value of 5, and thus, the electrical activity monitored forSite 1 indicates phrenic nerve stimulation. As depicted, none, or not asignificant portion, of the electrical activity monitored on theanterior side of the patient's torso during pacing therapy for Site 2exceeds a normalized threshold value of 5, and thus, the electricalactivity monitored for Site 2 does not indicate phrenic nervestimulation.

The techniques described in this disclosure, including those attributedto the IMD 16, the programmer 24, the computing apparatus 140, and/orvarious constituent components, may be implemented, at least in part, inhardware, software, firmware, or any combination thereof. For example,various aspects of the techniques may be implemented within one or moreprocessors, including one or more microprocessors, DSPs, ASICs, FPGAs,or any other equivalent integrated or discrete logic circuitry, as wellas any combinations of such components, embodied in programmers, such asphysician or patient programmers, stimulators, image processing devices,or other devices. The term “module,” “processor,” or “processingcircuitry” may generally refer to any of the foregoing logic circuitry,alone or in combination with other logic circuitry, or any otherequivalent circuitry.

Such hardware, software, and/or firmware may be implemented within thesame device or within separate devices to support the various operationsand functions described in this disclosure. In addition, any of thedescribed units, modules, or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components, orintegrated within common or separate hardware or software components.

When implemented in software, the functionality ascribed to the systems,devices and techniques described in this disclosure may be embodied asinstructions on a computer-readable medium such as RAM, ROM, NVRAM,EEPROM, FLASH memory, magnetic data storage media, optical data storagemedia, or the like. The instructions may be executed by one or moreprocessors to support one or more aspects of the functionality describedin this disclosure.

This disclosure has been provided with reference to illustrativeembodiments and is not meant to be construed in a limiting sense. Asdescribed previously, one skilled in the art will recognize that othervarious illustrative applications may use the techniques as describedherein to take advantage of the beneficial characteristics of theapparatus and methods described herein. Various modifications of theillustrative embodiments, as well as additional embodiments of thedisclosure, will be apparent upon reference to this description.

What is claimed:
 1. A non-invasive system for detecting phrenic nervestimulation during pacing therapy comprising: external electrodeapparatus comprising a plurality of external electrodes configured to belocated proximate tissue of a patient; and computing apparatus coupledto the external electrode apparatus and configured to: monitorelectrical activity using two or more external electrodes of theplurality of external electrodes during delivery of pacing therapy, anddetermine whether the patient's phrenic nerve is stimulated by thepacing therapy based on the monitored electrical activity.
 2. The systemof claim 1, wherein the two or more external electrodes of the pluralityof external electrodes are configured to be located on the anteriortorso of the patient.
 3. The system of claim 1, wherein the externalelectrode apparatus comprises one of a band and a vest configured to beworn about the torso of the patient, wherein the plurality of externalelectrodes are coupled to the band or vest.
 4. The system of claim 1,wherein monitoring electrical activity using two or more externalelectrodes of the plurality of external electrodes during delivery ofpacing therapy comprises monitoring electrical activity using two ormore external electrodes of the plurality of external electrodes for aselected time period after delivery of a pacing pulse.
 5. The system ofclaim 1, wherein determining whether the patient's phrenic nerve isstimulated by the pacing therapy comprises comparing a maximumpeak-to-peak amplitude of the monitored electrical activity to athreshold value.
 6. The system of claim 5, wherein the threshold valueis based on baseline measurements monitored using one or more externalelectrodes of the plurality of external electrodes during one ofintrinsic rhythm and atrial pacing, wherein the threshold value isgreater than or equal to 3 times a baseline value based on the baselinemeasurements.
 7. The system of claim 1, wherein determining whether thepatient's phrenic nerve is stimulated by the pacing therapy comprisesdetermining that the patient's phrenic nerve is stimulated if themonitored electrical activity from a selected percentage of the two ormore external electrodes used to monitor electrical activity duringdelivery of pacing therapy is indicative of phrenic nerve stimulation.8. A non-invasive method for detecting phrenic nerve stimulation duringpacing therapy comprising: monitoring electrical activity using two ormore external electrodes of a plurality of external electrodes duringdelivery of pacing therapy, wherein the plurality of external electrodeslocated proximate tissue of the patient; and determining whether thepatient's phrenic nerve is stimulated by the pacing therapy based on themonitored electrical activity.
 9. The method of claim 8, wherein the twoor more external electrodes of the plurality of external electrodes areconfigured to be located on the anterior torso of the patient.
 10. Themethod of claim 8, wherein monitoring electrical activity using two ormore external electrodes of the plurality of external electrodes duringdelivery of pacing therapy comprises monitoring electrical activityusing two or more external electrodes of the plurality of externalelectrodes for a selected time period after delivery of a pacing pulse.11. The method of claim 8, wherein determining whether the patient'sphrenic nerve is stimulated by the pacing therapy comprises comparing amaximum peak-to-peak amplitude of the monitored electrical activity to athreshold value.
 12. The method of claim 11, wherein the threshold valueis based on baseline measurements monitored using one or more externalelectrodes of the plurality of external electrodes during one ofintrinsic rhythm and atrial pacing, wherein the threshold value isgreater than or equal to 3 times a baseline value based on the baselinemeasurements.
 13. The method of claim 8, wherein determining whether thepatient's phrenic nerve is stimulated by the pacing therapy comprisesdetermining that the patient's phrenic nerve is stimulated if themonitored electrical activity from a selected percentage of the two ormore external electrodes used to monitor electrical activity duringdelivery of pacing therapy is indicative of phrenic nerve stimulation.14. A non-invasive system for detecting phrenic nerve stimulation duringpacing therapy comprising: electrode means for monitoring electricalactivity of a patient during delivery of pacing therapy, wherein theelectrode means comprises two or more external electrodes configured tobe located on the anterior torso of the patient; and computing means fordetermining whether the patient's phrenic nerve is stimulated by thepacing therapy based on monitored electrical activity.
 15. Anon-invasive system for use in detecting phrenic nerve stimulationduring pacing therapy using one or more pacing electrodes of a pluralityof pacing electrodes defining one or more of electrical pacing vectors,the system comprising: external electrode apparatus comprising aplurality of external electrodes configured to be located proximatetissue of a patient; display apparatus comprising a graphical userinterface, wherein the graphical user interface is configured to presentinformation for use in assisting a user in at least one of evaluatingpacing therapy and configuring pacing therapy; and computing apparatuscoupled to the external electrode apparatus and display apparatus andconfigured to: monitor electrical activity using two or more externalelectrodes of the plurality of external electrodes during delivery ofpacing therapy using each electrical pacing vector of one or moreelectrical pacing vectors, determine whether the patient's phrenic nerveis stimulated by the pacing therapy delivered using each electricalpacing vector of the one or more electrical pacing vectors based on themonitored electrical activity, and display, on the graphical userinterface, phrenic nerve stimulation information for the one or moreelectrical pacing vectors for use in assisting a user in at least one ofevaluating pacing therapy and configuring pacing therapy.
 16. The systemof claim 15, wherein the two or more electrodes of the plurality ofexternal electrodes are configured to be located on the anterior torsoof the patient.
 17. The system of claim 15, wherein the externalelectrode apparatus comprises one of a band and a vest configured to beworn about the torso of the patient, wherein the plurality of externalelectrodes are coupled to the band or vest.
 18. The system of claim 15,wherein monitoring electrical activity using two or more externalelectrodes of the plurality of external electrodes during delivery ofpacing therapy comprises monitoring electrical activity using two ormore external electrodes of the plurality of external electrodes for aselected time period after delivery of a pacing pulse.
 19. The system ofclaim 15, wherein determining whether the patient's phrenic nerve isstimulated by the pacing therapy comprises comparing a maximumpeak-to-peak amplitude of the monitored electrical activity to athreshold value.
 20. The system of claim 15, wherein determining whetherthe patient's phrenic nerve is stimulated by the pacing therapycomprises determining that the patient's phrenic nerve is stimulated ifthe monitored electrical activity from a selected percentage of the twoor more external electrodes used to monitor electrical activity duringdelivery of pacing therapy is indicative of phrenic nerve stimulation.21. The system of claim 15, wherein the computing apparatus is furtherconfigured to display, on the graphical user interface, phrenic nervestimulation information for the one or more electrical pacing vectorsproximate a graphical depiction of at least a portion of anatomy of thepatient's heart.
 22. The system of claim 15, wherein the delivery ofpacing therapy using each electrical pacing vector of one or moreelectrical pacing vectors comprises delivery of pacing therapy usingeach electrical pacing vector configured in each power configuration ofa plurality of different power configurations, wherein the computingapparatus is further configured to display, on the graphical userinterface, power configuration information for at least each electricalpacing vector of the one or more electrical pacing vectors that isdetermined to stimulate the patient's phrenic nerve.